臺灣博碩士論文加值系統

急性肺損傷及急性呼吸窘迫症候這類的肺部發炎疾病，其急性期經常會伴隨肺泡和微血管間的屏障崩壞以及發炎相關的細胞激素與趨化激素的產生。葡萄糖胺，一種自然產生且高度聚集在結締組織的胺基單醣，是作為關節的補充物且被廣泛運用在關節炎的治療上。近來，葡萄糖胺已開始因其潛在的抗發炎特質而被運用在治療某些發炎疾病上，並因具有抗細胞生長的能力而進一步發現會影響細胞的生理活動。然而，葡萄糖胺在肺部病理及生理上的角色及其參與的分子機制尚未充分清楚。本研究的目標就是要釐清葡萄糖胺在對細菌內毒素的反應下，如何扮演一個抗發炎的角色及其可能在細胞生長上造成的細胞毒性。使用氣管內滴入脂多醣所誘發的大鼠肺部發炎模型，我們注意到葡萄糖胺可減緩肺部水腫和多形核顆粒球浸潤的情形以及細胞激素(TNF-alpha、IL-1 beta和IFN-gamma)、趨化激素(CINC-1、MIP-2和MCP-1)跟NO/iNOS在肺泡及肺部組織產生的情況。使用大鼠肺泡上皮細胞株L2，也發現細胞激素混合物所調控的趨化激素(CINC-1和MIP-2)及NO/iNOS可被葡萄糖胺所抑制。我們更進一步證明葡萄糖胺所導致NO/iNOS的減少是透過對NF-kappaB訊息路徑的調降。除此之外，我們也發現葡萄糖胺對人類肺泡上皮細胞A549及人類支氣管上皮細胞HBECs，產生抑制細胞增生、細胞週期停滯及晚期細胞凋亡的效果。另外我們更證實葡萄糖胺可抑制視網膜母細胞瘤蛋白及影響細胞週期相關的調控蛋白(p21、p27、p53和HO-1)的表現。而且葡萄糖胺還經由蛋白酶體所造成的蛋白降解路徑來減弱p21的蛋白穩定性並誘發p21的核聚集。總而言之，葡萄糖胺至少有部分是透過影響NF-kappaB的訊息傳遞路徑而使其在脂多醣所誘發的肺部發炎中扮演抗發炎的角色，並藉由對視網膜母細胞瘤蛋白的減少以及對p21、p53和HO-1表現的調控與p21在核內的聚集，來造成細胞凋亡和使細胞週期停滯在G0/G1期，因而進一步對細胞增生造成抑制的情形。

Acute phase of lung inflammatory diseases, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), is usually accompanied with disruption of alveolar-capillary barrier and induction of inflammatory-related cytokines and chemokines. Glucosamine, a natural occurring amino monosaccharide highly concentrated in connective tissues, is a joint supplement widely used in the treatment of arthritis. Recently, glucosamine has begun to be considered the potential anti-inflammatory properties to treat the other inflammation disease and anti-cell proliferation abilities to affect cell physiological activities. Nevertheless, the roles of glucosamine in lung pathology and physiology as well as the involved molecular mechanisms have not been well characterized. Our study aims to clarify how glucosamine plays an anti-inflammatory role in response to bacterial endotoxin and the additional possible toxicity on cellular proliferation. Using rat lung inflammation model caused by intratracheal instillation of LPS, pulmonary edema and polymorphonuclear neutrophil (PMN) infiltration, as well as the production of inflammatory cytokines (TNF-alpha, IL-1 beta and IFN-gamma), chemokines (CINC-1, MIP-2 and MCP-1) and nitric oxide (NO)/inducible nitric oxide synthase (iNOS) in alveolar space and/or lung parenchyma, were noted to be mitigated by glucosamine. Using a rat alveolar epithelial cell line L2, cytokine mixture (cytomix)-regulated expression of chemokines (CINC-1 and MIP-2) and NO/iNOS was also suppressed by glucosamine. In addition, we further to prove that glucosamine-reduced NO/iNOS is through down-regulation of NF-kappaB signaling cascades. Furthermore, we also uncovered that glucosamine suppressed cellular proliferation, and induced cell cycle arrest and late apoptosis in human alveolar epithelial cells (A549) and bronchial epithelial cells (HBECs). Moreover, we found an inhibitory effect on phosphorylation of retinoblastoma (Rb) protein and modification on expression of cell cycle-related regulators (p21, p27, p53 and HO-1). In addition, glucosamine attenuated p21 protein stability via the proteasomal proteolytic pathway, as well as inducing p21 nuclear accumulation. Taken together, glucosamine appears to act as an anti-inflammatory role in LPS-induced lung inflammation, at least in part, by targeting to the NF-kappaB signaling pathway, and an inhibitory molecule on cell proliferation through apoptosis and cell cycle disturbance with a halt at G0/G1 phase, which is partly mediated by the reduction in Rb phosphorylation together with modulation of p21, p53 and HO-1 expression, and nuclear p21 accumulation.

ACKNOWLEDGEMENTS 4
LIST OF FIGURES AND TABLES 5
ENGLISH ABSTRACT 9
CHINESE ABSTRACT 11
CHAPTER
I. INTRODUCTION 13
1. Significance of lung immunity 14
1.1. The inflammation in lung 14
1.2. Inflammation-related mediators in acute lung inflammation 16
1.3. Inflammatory cells recruitment in acute lung inflammation 22
2. Cell cycle 26
2.1. Roles beyond cell cycle regulation 26
2.2. Other cell cycle regulatory molecules 29
3. Glucosamine 33
3.1. Pharmacological properties of glucosamine 34
3.2. Anti-inflammatory abilities of glucosamine 35
3.3. Anti-cell proliferation activities of glucosamine 37
4. Overall hypothesis and research goals of this thesis 38
II. MATERIALS AND MATHODS 40
1. Chemicals and reagents 41
2. Cell culture 42
3. Animals 42
4. Exposure of L2 cells to glucosamine and cytokines or A549 and HBECs to glucosamine 42
5. Animal acute lung inflammation model 43
6. Preparation of bronchoalveolar lavage and lung tissues 43
7. Measurement of the lung wet/dry weight ratio 44
8. Analysis of total protein concentration and cell count of the BALF 44
9. Culture of the cells collected from the BALF 45
10. Measurement of inflammatory cytokines 45
11. Immunohistochemical analysis 46
12. Nitrite determination 47
13. Transfection and analysis of iNOS promoter activity and NF-kB reporter activity 47
14. Determination of cell viability 48
15. Cell cycle and apoptosis analyses 48
16. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) 49
17. Western blot analysis 50
18. Statistical analysis 50
III. RESULTS 52
1. The impact of glucosamine on LPS-induced acute lung inflammation 53
2. The effects of glucosamine on LPS-elicited inflammatory mediator secretion in the BALF and the cultured medium containing BALF cells, and LPS-induced mRNA expression of inflammatory mediators in the lung 54
3. The influence of glucosamine on LPS-induced protein and mRNA expression of iNOS in lung tissue and the NO level in the cultured medium containing BALF cells 55
4. The impact of Glucosamine on LPS-induced chemokine expression, chemokine production, NO production and iNOS expression during pulmonary inflammation in vitro 56
5. The NF-kB pathway as a target for glucosamine mitigating cytomix-elicited NO production and iNOS protein expression 57
6. The impacts of glucosamine on cell proliferation, cell cycle distribution and cell apoptosis 60
7. The impact of glucosamine on Rb protein phosphorylation 62
8. Modulation of glucosamine on p21, p53 and HO-1, but not p27 protein expression 62
9. Glucosamine-induced expression of p21, p53 and HO-1 mRNA in A549 cells, and HO-1 mRNA in HBECs 63
10. Glucosamine-triggered reduction of cellular p21 protein stability and promotion of nuclear p21 translocation 64
IV. DISCUSSION AND CONCLUSION 66
V. REVIEW AND FUTURE RESEARCH DIRECTION 83
1. Review 84
2. Future research direction 86
REFERENCES 130
Figure 1 The impacts of glucosamine on LPS-induced pulmonary edema and neutrophil influx 90
Figure 2 The influence of glucosamine on LPS-induced cytokine and chemokine production in the BALF and the cultured medium of the BALF cells 92
Figure 3 The impacts of glucosamine on the mRNA expression of LPS-elicited inflammatory mediators in the lung 94
Figure 4 The effects of glucosamine on LPS-mediated iNOS expression in the lung tissue and the NO production in the conditioned medium containing BALF cells 96
Figure 5 The impacts of glucosamine on cytomix-induced production and mRNA expression of CINC-1 and MIP-2 in L2 cells 98
Figure 6 Alleviation of cytomix-elicited NO release and expression of iNOS protein and mRNA by glucosamine in L2 cells after glucosamine administration in L2 cells 100
Figure 7 The reduction of cytomix-stimulated iNOS promoter activity and the changes in the stability of iNOS mRNA caused by glucosamine treatment of L2 cells 102
Figure 8 Involvement of various signaling pathways in cytomix-induced NO production and iNOS protein expression in L2 cells 104
Figure 9 Attenuation of cytomix-induced IkB phosphorylation, nuclear p65 accumulation and NF-kB reporter activation by glucosamine in L2 cells 106
Figure 10 The reverse of suppressed effect caused by glucosamine on cytomix-mediated NO production and iNOS expression in L2 cells 108
Figure 11 Inhibition of cell proliferation by glucosamine in A549 cells and HBECs 110
Figure 12 Changes in cell cycle distribution in A549 cells and HBECs by glucosamine 112
Figure 13 Glucosamine-induced apoptosis in A549 cells and HBECs 114
Figure 14 Effects of glucosamine on Rb protein phosphorylation in A549 cells and HBECs 116
Figure 15 Regulation of protein expression of p21, p27, p53 and HO-1 in A549 cells by glucosamine 118
Figure 16 Regulation of protein expression of p21, p27, p53 and HO-1 in HBECs 120
Figure 17 Effects of glucosamine on p21, p27, p53 and HO-1 mRNA expression in A549 cells 122
Figure 18 Effects of glucosamine on p21, p27, p53 and HO-1 mRNA expression in HBECs 124
Figure 19 Effects of glucosamine on cellular p21 protein stability and nuclear translocation in HBECs 126
Figure 20 The overall impact of glucosamine on acute lung inflammation and cell proliferation confirmed in our study 128

Table 1 Primers used and the sizes of PCR products 129

Allison DF, Wamsley JJ, Kumar M, Li D, Gray LG, Hart GW, Jones DR, Mayo MW 2012 Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-kappaB acetylation and transcription. Proc Natl Acad Sci U S A 109:16888-16893
Amador V, Ge S, Santamaria PG, Guardavaccaro D, Pagano M 2007 APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell 27:462-473
Amano H, Morimoto K, Senba M, Wang H, Ishida Y, Kumatori A, Yoshimine H, Oishi K, Mukaida N, Nagatake T 2004 Essential contribution of monocyte chemoattractant protein-1/C-C chemokine ligand-2 to resolution and repair processes in acute bacterial pneumonia. J Immunol 172:398-409
Bach EA, Aguet M, Schreiber RD 1997 The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563-591
Baggiolini M, Dewald B, Moser B 1994 Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol 55:97-179
Baggiolini M, Imboden P, Detmers P 1992 Neutrophil activation and the effects of interleukin-8/neutrophil-activating peptide 1 (IL-8/NAP-1). Cytokines 4:1-17
Baggiolini M, Loetscher P, Moser B 1995 Interleukin-8 and the chemokine family. Int J Immunopharmacol 17:103-108
Baggiolini M, Walz A, Kunkel SL 1989 Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045-1049
Barclay TS, Tsourounis C, McCart GM 1998 Glucosamine. Ann Pharmacother 32:574-579
Barratt GM, Raddassi K, Petit JF, Tenu JP 1991 MDP and LPS act synergistically to induce arginine-dependent cytostatic activity in rat alveolar macrophages. Int J Immunopharmacol 13:159-165
Beck-Schimmer B, Madjdpour C, Kneller S, Ziegler U, Pasch T, Wuthrich RP, Ward PA, Schimmer RC 2002 Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation. Eur Respir J 19:1142-1150
Bendjennat M, Boulaire J, Jascur T, Brickner H, Barbier V, Sarasin A, Fotedar A, Fotedar R 2003 UV irradiation triggers ubiquitin-dependent degradation of p21(WAF1) to promote DNA repair. Cell 114:599-610
Boehm U, Klamp T, Groot M, Howard JC 1997 Cellular responses to interferon-gamma. Annu Rev Immunol 15:749-795
Braham R, Dawson B, Goodman C 2003 The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med 37:45-49
Busse WW, Lemanske RF, Jr. 2001 Asthma. N Engl J Med 344:350-362
Cairns CB, Panacek EA, Harken AH, Banerjee A 2000 Bench to bedside: tumor necrosis factor-alpha: from inflammation to resuscitation. Acad Emerg Med 7:930-941
Canman CE, Gilmer TM, Coutts SB, Kastan MB 1995 Growth factor modulation of p53-mediated growth arrest versus apoptosis. Genes Dev 9:600-611
Capelli A, Di SA, Gnemmi I, Balbo P, Cerutti CG, Balbi B, Lusuardi M, Donner CF 1999 Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics. Eur Respir J 14:160-165
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B 1975 An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 72:3666-3670
Chan ED, Riches DW 2001 IFN-gamma + LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38(mapk) in a mouse macrophage cell line. Am J Physiol Cell Physiol 280:C441-C450
Chang YH, Horng CT, Chen YH, Chen PL, Chen CL, Liang CM, Chien MW, Chen JT 2008 Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. Invest Ophthalmol Vis Sci 49:5441-5449
Chau BN, Wang JY 2003 Coordinated regulation of life and death by RB. Nat Rev Cancer 3:130-138
Chen ES, Greenlee BM, Wills-Karp M, Moller DR 2001 Attenuation of lung inflammation and fibrosis in interferon-gamma-deficient mice after intratracheal bleomycin. Am J Respir Cell Mol Biol 24:545-555
Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE 2007 Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappaB in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol 179:6097-6106
Chen JT, Chen CH, Horng CT, Chien MW, Lu DW, Liang JB, Tai MC, Chang YH, Chen PL, Chen YH 2006a Glucosamine sulfate inhibits proinflammatory cytokine-induced icam-1 production in human conjunctival cells in vitro. J Ocul Pharmacol Ther 22:402-416
Chen JT, Chen PL, Chang YH, Chien MW, Chen YH, Lu DW 2006b Glucosamine sulfate inhibits leukocyte adhesion in response to cytokine stimulation of retinal pigment epithelial cells in vitro. Exp Eye Res 83:1052-1062
Chen JT, Liang JB, Chou CL, Chien MW, Shyu RC, Chou PI, Lu DW 2006c Glucosamine sulfate inhibits TNF-alpha and IFN-gamma-induced production of ICAM-1 in human retinal pigment epithelial cells in vitro. Invest Ophthalmol Vis Sci 47:664-672
Chen X, Chi Y, Bloecher A, Aebersold R, Clurman BE, Roberts JM 2004 N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1). Mol Cell 16:839-847
Chesnokov V, Sun C, Itakura K 2009 Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling. Cancer Cell Int 9:25
Choi HC, Lee KY, Lee DH, Kang YJ 2009 Heme oxygenase-1 induced by aprotinin inhibits vascular smooth muscle cell proliferation through cell cycle arrest in hypertensive rats. Korean J Physiol Pharmacol 13:309-313
Chollet-Martin S, Montravers P, Gibert C, Elbim C, Desmonts JM, Fagon JY, Gougerot-Pocidalo MA 1994 Relationships between polymorphonuclear neutrophils and cytokines in patients with adult respiratory distress syndrome. Ann N Y Acad Sci 725:354-366
Chorley BN, Li Y, Fang S, Park JA, Adler KB 2006 (R)-albuterol elicits antiinflammatory effects in human airway epithelial cells via iNOS. Am J Respir Cell Mol Biol 34:119-127
Chung MJ, Park JK, Park YI 2012 Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides in IgE-antigen complex-stimulated RBL-2H3 cells and asthma model mice. Int Immunopharmacol 12:453-459
Coqueret O 2003 New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol 13:65-70
Couillin I, Vasseur V, Charron S, Gasse P, Tavernier M, Guillet J, Lagente V, Fick L, Jacobs M, Coelho FR, Moser R, Ryffel B 2009 IL-1R1/MyD88 signaling is critical for elastase-induced lung inflammation and emphysema. J Immunol 183:8195-8202
Crolle G, D'Este E 1980 Glucosamine sulphate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 7:104-109
Curtis LM, Agarwal A 2007 HOpe for contrast-induced acute kidney injury. Kidney Int 72:907-909
Dahmer S, Schiller RM 2008 Glucosamine. Am Fam Physician 78:471-476
D'Ambrosio E, Casa B, Bompani R, Scali G, Scali M 1981 Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 2:504-508
Danese S, Semeraro S, Armuzzi A, Papa A, Gasbarrini A 2006 Biological therapies for inflammatory bowel disease: research drives clinics. Mini Rev Med Chem 6:771-784
Decker T, Stockinger S, Karaghiosoff M, Muller M, Kovarik P 2002 IFNs and STATs in innate immunity to microorganisms. J Clin Invest 109:1271-1277
DeGregori J 2002 The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta 1602:131-150
Dinarello CA 1996 Biologic basis for interleukin-1 in disease. Blood 87:2095-2147
Dinarello CA 2001 Anti-cytokine therapies in response to systemic infection. J Investig Dermatol Symp Proc 6:244-250
Driscoll B, Wu L, Buckley S, Hall FL, Anderson KD, Warburton D 1997 Cyclin D1 antisense RNA destabilizes pRb and retards lung cancer cell growth. Am J Physiol 273:L941-L949
Du Q, Zhang X, Cardinal J, Cao Z, Guo Z, Shao L, Geller DA 2009 Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res 69:3764-3771
Du Bois RM 2010 Strategies for treating idiopathic pulmonary fibrosis. Nat Rev Drug Discov 9:129-140
Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, Clinton WR, Lee ME, Nabel GJ, Nabel EG 2001 Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 7:693-698
Durante W 2003 Heme oxygenase-1 in growth control and its clinical application to vascular disease. J Cell Physiol 195:373-382
Edelson PJ, Cohn ZA 1973 Peroxidase-mediated mammalian cell cytotoxicity. J Exp Med 138:318-323
El-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW, Vogelstein B 1994 WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54:1169-1174
El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B 1993 WAF1, a potential mediator of p53 tumor suppression. Cell 75:817-825
El-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, Hill DE, Healy E, Rees JL, Hamilton SR, Kinzler KW, Vogelstein B 1995 Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res 55:2910-2919
Ellis TN, Beaman BL 2004 Interferon-gamma activation of polymorphonuclear neutrophil function. Immunology 112:2-12
Faggioni R, Fantuzzi G, Fuller J, Dinarello CA, Feingold KR, Grunfeld C 1998 IL-1 beta mediates leptin induction during inflammation. Am J Physiol 274:R204-R208
Fang C, Peng M, Li G, Tian J, Yin D 2007 New functions of glucosamine as a scavenger of the lipid peroxidation product malondialdehyde. Chem Res Toxicol 20:947-953
Felson DT 2007 Chondroitin for pain in osteoarthritis. Ann Intern Med 146:611-612
Ferguson KL, Slack RS 2001 The Rb pathway in neurogenesis. Neuroreport 12:A55-A62
Forstermann U, Gath I, Schwarz P, Closs EI, Kleinert H 1995 Isoforms of nitric oxide synthase. Properties, cellular distribution and expressional control. Biochem Pharmacol 50:1321-1332
Freeman BA, Crapo JD 1982 Biology of disease: free radicals and tissue injury. Lab Invest 47:412-426
Frucht DM, Fukao T, Bogdan C, Schindler H, O'Shea JJ, Koyasu S 2001 IFN-gamma production by antigen-presenting cells: mechanisms emerge. Trends Immunol 22:556-560
Galea CA, Nourse A, Wang Y, Sivakolundu SG, Heller WT, Kriwacki RW 2008 Role of intrinsic flexibility in signal transduction mediated by the cell cycle regulator, p27 Kip1. J Mol Biol 376:827-838
Gartel AL, Tyner AL 1999 Transcriptional regulation of the p21 (WAF1/CIP1) gene. Exp Cell Res 246:280-289
Gartel AL, Tyner AL 2002 The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther 1:639-649
Geiser T, Atabai K, Jarreau PH, Ware LB, Pugin J, Matthay MA 2001 Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism. Am J Respir Crit Care Med 163:1384-1388
Gonzalez-Michaca L, Farrugia G, Croatt AJ, Alam J, Nath KA 2004 Heme: a determinant of life and death in renal tubular epithelial cells. Am J Physiol Renal Physiol 286:F370-F377
Goodman RB, Pugin J, Lee JS, Matthay MA 2003 Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev 14:523-535
Goodman RB, Strieter RM, Frevert CW, Cummings CJ, Tekamp-Olson P, Kunkel SL, Walz A, Martin TR 1998 Quantitative comparison of C-X-C chemokines produced by endotoxin-stimulated human alveolar macrophages. Am J Physiol 275:L87-L95
Goodman RB, Strieter RM, Martin DP, Steinberg KP, Milberg JA, Maunder RJ, Kunkel SL, Walz A, Hudson LD, Martin TR 1996 Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med 154:602-11
Gorgoulis VG, Zacharatos P, Kotsinas A, Mariatos G, Liloglou T, Vogiatzi T, Foukas P, Rassidakis G, Garinis G, Ioannides T, Zoumpourlis V, Bramis J, Michail PO, Asimacopoulos PJ, Field JK, Kittas C 2000 Altered expression of the cell cycle regulatory molecules pRb, p53 and MDM2 exert a synergetic effect on tumor growth and chromosomal instability in non-small cell lung carcinomas (NSCLCs). Mol Med 6:208-237
Gouze JN, Gouze E, Popp MP, Bush ML, Dacanay EA, Kay JD, Levings PP, Patel KR, Saran JP, Watson RS, Ghivizzani SC 2006 Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta. Arthritis Res Ther 8:R173
Grashoff WF, Sont JK, Sterk PJ, Hiemstra PS, de Boer WI, Stolk J, Han J, van Krieken JM 1997 Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages. Am J Pathol 151:1785-1790
Graves DT, Jiang Y 1995 Chemokines, a family of chemotactic cytokines. Crit Rev Oral Biol Med 6:109-118
Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel EM, Waddell MB, Jakel H, Kullmann M, Kriwacki RW, Hengst L 2007 Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell 128:269-280
Gu L, Tseng SC, Rollins BJ 1999 Monocyte chemoattractant protein-1. Chem Immunol 72:7-29
Haas MJ, Wong NC, Mooradian AD 2004 Effect of glucosamine on apolipoprotein AI mRNA stabilization and expression in HepG2 cells. Metabolism 53:766-771
Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E, Fox MP, Wei N. 1995 Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell 6:387-400
He X, Mekasha S, Mavrogiorgos N, Fitzgerald KA, Lien E, Ingalls RR 2010 Inflammation and fibrosis during Chlamydia pneumoniae infection is regulated by IL-1 and the NLRP3/ASC inflammasome. J Immunol 184:5743-5754
Helt CE, Rancourt RC, Staversky RJ, O'Reilly MA 2001 p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced toxicity. Toxicol Sci 63:214-222
Henson PM, Johnston RB, Jr. 1987 Tissue injury in inflammation. Oxidants, proteinases, and cationic proteins. J Clin Invest 79:669-674
Hollstein M, Sidransky D, Vogelstein B, Harris CC 1991 p53 mutations in human cancers. Science 253:49-53
Holt PG, Strickland DH, Wikstrom ME, Jahnsen FL 2008 Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 8:142-152
Horsch M, Hoesch L, Vasella A, Rast DM 1991 N-acetylglucosaminono-1,5-lactone oxime and the corresponding (phenylcarbamoyl)oxime. Novel and potent inhibitors of beta-N-acetylglucosaminidase. Eur J Biochem 197:815-818
Hunter T, Pines J 1994 Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell 79:573-582
Iida M, Watanabe K, Tsurufuji M, Takaishi K, Iizuka Y, Tsurufuji S 1992 Level of neutrophil chemotactic factor CINC/gro, a member of the interleukin-8 family, associated with lipopolysaccharide-induced inflammation in rats. Infect Immun 60:1268-1272
Ito H, Koide N, Hassan F, Islam S, Tumurkhuu G, Mori I, Yoshida T, Kakumu S, Moriwaki H, Yokochi T 2006 Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock. Lab Invest 86:254-261
Ji DB, Xu B, Liu JT, Ran FX, Cui JR 2011 beta-Escin sodium inhibits inducible nitric oxide synthase expression via downregulation of the JAK/STAT pathway in A549 cells. Mol Carcinog 50:945-960
Jiang D, Liang J, Noble PW 2011 Hyaluronan as an immune regulator in human diseases. Physiol Rev 91:221-264
Jiang Y, Beller DI, Frendl G, Graves DT 1992 Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol 148:2423-2428
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW 1991 Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304-6311
Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ 1993 Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev 7:331-342
Kim CH, Cheong KA, Park CD, Lee AY 2011 Glucosamine improved atopic dermatitis-like skin lesions in NC/Nga mice by inhibition of Th2 cell development. Scand J Immunol 73:536-545
Kim CH, Choi YS, Cheong KA, Lee AY 2013 Mechanism underlying the effect of combined therapy using glucosamine and low-dose cyclosporine A on the development of atopic dermatitis-like skin lesions in NC/Nga mice. Int Immunopharmacol 15:424-432
Kirkham SG, Samarasinghe RK 2009 Review article: Glucosamine. J Orthop Surg (Hong Kong ) 17:72-76
Kleinert H, Euchenhofer C, Ihrig-Biedert I, Forstermann U 1996 In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of transcription factor NF-kappaB. J Biol Chem 271:6039-6044
Kleinert H, Pautz A, Linker K, Schwarz PM 2004 Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500:255-266
Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J 2001 Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 107:1529-1536
Krogsboll LT, Hrobjartsson A, Gotzsche PC 2009 Spontaneous improvement in randomised clinical trials: meta-analysis of three-armed trials comparing no treatment, placebo and active intervention. BMC Med Res Methodol 9:1
Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB 1992 Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A 89:7491-7495
Kumar D, Bhaskaran M, Alagappan L, Tori D, Yadav I, Konkimalla S, Magoon S, Singhal PC 2010 Heme oxygenase-1 modulates mesangial cell proliferation by p21 Waf1 upregulation. Ren Fail 32:254-258
Kumar H, Kawai T, Akira S 2009 Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388:621-625
Kwon S, George SC 1999 Synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells. Nitric Oxide 3:348-357
Lafferty EI, Qureshi ST, Schnare M 2010 The role of toll-like receptors in acute and chronic lung inflammation. J Inflamm (Lond) 7:57
Lee H, Pespeni M, Roux J, Dennery PA, Matthay MA, Pittet JF 2005 HO-1 induction restores c-AMP-dependent lung epithelial fluid transport following severe hemorrhage in rats. FASEB J 19:287-289
Lee JY, Kim HS, Kim JY, Sohn J 2009 Nuclear translocation of p21(WAF1/CIP1) protein prior to its cytosolic degradation by UV enhances DNA repair and survival. Biochem Biophys Res Commun 390:1361-1366
Lee PJ, Alam J, Sylvester SL, Inamdar N, Otterbein L, Choi AM 1996a Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury. Am J Respir Cell Mol Biol 14:556-568
Lee PJ, Alam J, Wiegand GW, Choi AM 1996b Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc Natl Acad Sci U S A 93:10393-10398
Li MD, Ruan HB, Singh JP, Zhao L, Zhao T, Azarhoush S, Wu J, Evans RM, Yang X 2012 O-GlcNAc transferase is involved in glucocorticoid receptor-mediated transrepression. J Biol Chem 287:12904-12912
Liang CM, Tai MC, Chang YH, Chen YH, Chen CL, Chien MW, Chen JT 2010 Glucosamine inhibits epidermal growth factor-induced proliferation and cell-cycle progression in retinal pigment epithelial cells. Mol Vis 16:2559-2571
Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM 1995 Human Mig chemokine: biochemical and functional characterization. J Exp Med 182:1301-1314
Lin YC, Liang YC, Sheu MT, Lin YC, Hsieh MS, Chen TF, Chen CH 2008 Chondroprotective effects of glucosamine involving the p38 MAPK and Akt signaling pathways. Rheumatol Int 28:1009-1016
Lincet H, Poulain L, Remy JS, Deslandes E, Duigou F, Gauduchon P, Staedel C 2000 The p21(cip1/waf1) cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells. Cancer Lett 161:17-26
Liu BQ, Meng X, Li C, Gao YY, Li N, Niu XF, Guan Y, Wang HQ 2011 Glucosamine induces cell death via proteasome inhibition in human ALVA41 prostate cancer cell. Exp Mol Med 43:487-493
Liu PY, Chan JY, Lin HC, Wang SL, Liu ST, Ho CL, Chang LC, Huang SM 2008 Modulation of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene by Zac1 through the antagonistic regulators p53 and histone deacetylase 1 in HeLa Cells. Mol Cancer Res 6:1204-1214
Lowe SW, Ruley HE, Jacks T, Housman DE 1993 p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957-967
Lu Z, Hunter T 2010 Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell Cycle 9:2342-2352
Madjdpour L, Kneller S, Booy C, Pasch T, Schimmer RC, Beck-Schimmer B 2003 Acid-induced lung injury: role of nuclear factor-kappaB. Anesthesiology 99:1323-1332
Maines MD 1988 Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557-2568
Martin TR, Pistorese BP, Hudson LD, Maunder RJ 1991 The function of lung and blood neutrophils in patients with the adult respiratory distress syndrome. Implications for the pathogenesis of lung infections. Am Rev Respir Dis 144:254-262
Masson E, Wiernsperger N, Lagarde M, El Bawab S 2005 Glucosamine induces cell-cycle arrest and hypertrophy of mesangial cells: implication of gangliosides. Biochem J 388:537-544
McAlindon TE, LaValley MP, Gulin JP, Felson DT 2000 Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 283:1469-1475
Mcquire WW, Spragg RG, Cohen AB, Cochrane CG 1982 Studies on the pathogenesis of the adult respiratory distress syndrome. J Clin Invest 69:543-553
Mehta S 2005 The effects of nitric oxide in acute lung injury. Vascul Pharmacol 43:390-403
Meininger CJ, Kelly KA, Li H, Haynes TE, Wu G 2000 Glucosamine inhibits inducible nitric oxide synthesis. Biochem Biophys Res Commun 279:234-239
Meldrum DR 1998 Tumor necrosis factor in the heart. Am J Physiol 274:R577-R595
Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG 1999 The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309-313
Milberg JA, Davis DR, Steinberg KP, Hudson LD 1995 Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA 273:306-309
Mizgerd JP 2006 Lung infection--a public health priority. PLoS Med 3:e76
Morgan DO 1995 Principles of CDK regulation. Nature 374:131-134
Moxley MA, Baird TL, Corbett JA 2000 Adoptive transfer of acute lung injury. Am J Physiol Lung Cell Mol Physiol 279:L985-L993
Mukhopadhyay S, Hoidal JR, Mukherjee TK 2006 Role of TNFalpha in pulmonary pathophysiology. Respir Res 7:125
Myers SJ, Wong LM, Charo IF 1995 Signal transduction and ligand specificity of the human monocyte chemoattractant protein-1 receptor in transfected embryonic kidney cells. J Biol Chem 270:5786-5792
Nakagawa H, Ando Y, Takano K, Sunada Y 1998 Differential production of chemokines and their role in neutrophil infiltration in rat allergic inflammation. Int Arch Allergy Immunol 115:137-143
Nakagawa H, Komorita N, Shibata F, Ikesue A, Konishi K, Fujioka M, Kato H 1994 Identification of cytokine-induced neutrophil chemoattractants (CINC), rat GRO/CINC-2 alpha and CINC-2 beta, produced by granulation tissue in culture: purification, complete amino acid sequences and characterization. Biochem J 301 ( Pt 2):545-550
Nakamura H, Masuko K, Yudoh K, Kato T, Kamada T, Kawahara T 2007 Effects of glucosamine administration on patients with rheumatoid arthritis. Rheumatol Int 27:213-218
Nelson S, Mason CM, Kolls J, Summer WR 1995 Pathophysiology of pneumonia. Clin Chest Med 16:1-12
Neumann B, Emmanuilidis K, Stadler M, Holzmann B 1998 Distinct functions of interferon-gamma for chemokine expression in models of acute lung inflammation. Immunology 95:512-521
Nevins JR 2001 The Rb/E2F pathway and cancer. Hum Mol Genet 10:699-703
Niederman MS, Fein AM 1990 Sepsis syndrome, the adult respiratory distress syndrome, and nosocomial pneumonia. A common clinical sequence. Clin Chest Med 11:633-656
Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T 2008 CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem 283:29045-29052
Nuesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, Egger M, Juni P 2010 Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ 341:c3515
Nurse P 2000 A long twentieth century of the cell cycle and beyond. Cell 100:71-78
Offer S, Shoseyov D, Bibi H, Eliraz A, Madar Z 2003 A leukotriene receptor antagonist modulates iNOS in the lung and in a leukotriene-free cell model. Nitric Oxide 9:10-17
Olman MA, White KE, Ware LB, Simmons WL, Benveniste EN, Zhu S, Pugin J, Matthay MA 2004 Pulmonary edema fluid from patients with early lung injury stimulates fibroblast proliferation through IL-1 beta-induced IL-6 expression. J Immunol 172:2668-2677
Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR 2001 Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 164:1896-1903
Parsons PE, Fowler AA, Hyers TM, Henson PM 1985 Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome. Am Rev Respir Dis 132:490-493
Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC 2002 Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 162:2113-2123
Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS, Piwnica-Worms H 1997 Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 277:1501-1505
Pittet JF, Mackersie RC, Martin TR, Matthay MA 1997 Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155:1187-1205
Poljakovic M, Nygren JM, Persson K 2003 Signalling pathways regulating inducible nitric oxide synthase expression in human kidney epithelial cells. Eur J Pharmacol 469:21-28
Pugin J, Ricou B, Steinberg KP, Suter PM, Martin TR 1996 Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1. Am J Respir Crit Care Med 153:1850-1856
Pujalte JM, Llavore EP, Ylescupidez FR 1980 Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 7:110-114
Quinton LJ, Nelson S, Zhang P, Boe DM, Happel KI, Pan W, Bagby GJ 2004 Selective transport of cytokine-induced neutrophil chemoattractant from the lung to the blood facilitates pulmonary neutrophil recruitment. Am J Physiol Lung Cell Mol Physiol 286:L465-L472
Rafi MM, Yadav PN, Rossi AO 2007 Glucosamine inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage cells (RAW 264.7) by inhibition of p38-MAP kinase and transcription factor NF-kappaB. Mol Nutr Food Res 51:587-593
Ravichandran K, Tyagi A, Deep G, Agarwal C, Agarwal R 2011 Interleukin-1beta-induced iNOS expression in human lung carcinoma A549 cells: involvement of STAT and MAPK pathways. Indian J Exp Biol 49:840-847
Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C 2001 Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 357:251-256
Repine JE, Beehler CJ 1991 Neutrophils and adult respiratory distress syndrome: two interlocking perspectives in 1991. Am Rev Respir Dis 144:251-252
Rodriguez-Vilarrupla A, Diaz C, Canela N, Rahn HP, Bachs O, Agell N 2002 Identification of the nuclear localization signal of p21(cip1) and consequences of its mutation on cell proliferation. FEBS Lett 531:319-323
Runkel DR, Cupp MJ 1999 Glucosamine sulfate use in osteoarthritis. Am J Health Syst Pharm 56:267-269
Russo AA, Jeffrey PD, Patten AK, Massague J, Pavletich NP 1996 Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 382:325-331
Ryter SW, Alam J, Choi AM 2006 Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 86:583-650
Sack M 2002 Tumor necrosis factor-alpha in cardiovascular biology and the potential role for anti-tumor necrosis factor-alpha therapy in heart disease. Pharmacol Ther 94:123-135
Sarzi-Puttini P, Atzeni F, Shoenfeld Y, Ferraccioli G 2005 TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma. Autoimmun Rev 4:153-161
Schmidt R, Hoetzel A, Baechle T, Loop T, Humar M, Bauer M, Pahl HL, Geiger KK, Pannen BH 2004 Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo. J Hepatol 41:706-713
Schroder K, Hertzog PJ, Ravasi T, Hume DA 2004 Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163-189
Schurr JR, Young E, Byrne P, Steele C, Shellito JE, Kolls JK 2005 Central role of toll-like receptor 4 signaling and host defense in experimental pneumonia caused by Gram-negative bacteria. Infect Immun 73:532-545
Scotto dA, Politi L, Giordano C, Scandurra R 2010 A peptidyl-glucosamine derivative affects IKKalpha kinase activity in human chondrocytes. Arthritis Res Ther 12:R18
Setnikar I, Giachetti C, Zanolo G 1984 Absorption, distribution and excretion of radioactivity after a single intravenous or oral administration of [14C] glucosamine to the rat. Pharmatherapeutica 3:538-550
Setnikar I, Giacchetti C, Zanolo G 1986 Pharmacokinetics of glucosamine in the dog and in man. Arzneimittelforschung 36:729-735
Setnikar I, Palumbo R, Canali S, Zanolo G 1993 Pharmacokinetics of glucosamine in man. Arzneimittelforschung 43:1109-1113
Sherr CJ, Roberts JM 1999 CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501-1512
Sheaff RJ, Singer JD, Swanger J, Smitherman M, Roberts JM, Clurman BE 2000 Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination. Mol Cell 5:403-410
Shibata MA, Yoshidome K, Shibata E, Jorcyk CL, Green JE 2001 Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. Cancer Gene Ther 8:23-35
Sionov RV, Haupt Y 1999 The cellular response to p53: the decision between life and death. Oncogene 18:6145-6157
Standiford TJ, Kunkel SL, Phan SH, Rollins BJ, Strieter RM 1991 Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells. J Biol Chem 266:9912-9918
Standiford TJ, Rolfe MW, Kunkel SL, Lynch JP, III, Burdick MD, Gilbert AR, Orringer MB, Whyte RI, Strieter RM 1993 Macrophage inflammatory protein-1 alpha expression in interstitial lung disease. J Immunol 151:2852-2863
Steinberg KP, Milberg JA, Martin TR, Maunder RJ, Cockrill BA, Hudson LD 1994 Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med 150:113-122
Stevaux O, Dyson NJ 2002 A revised picture of the E2F transcriptional network and RB function. Curr Opin Cell Biol 14:684-691
Stewart TE, Valenza F, Ribeiro SP, Wener AD, Volgyesi G, Mullen JB, Slutsky AS 1995 Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis. Am J Respir Crit Care Med 151:713-718
Su WY, Day BJ, Kang BH, Crapo JD, Huang YC, Chang LY 1996 Lung epithelial cell-released nitric oxide protects against PMN-mediated cell injury. Am J Physiol 271:L581-L586
Suzuki A, Tsutomi Y, Akahane K, Araki T, Miura M 1998 Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. Oncogene 17:931-939
Szilasi M, Dolinay T, Nemes Z, Strausz J 2006 Pathology of chronic obstructive pulmonary disease. Pathol Oncol Res 12:52-60
Taille C, Almolki A, Benhamed M, Zedda C, Megret J, Berger P, Leseche G, Fadel E, Yamaguchi T, Marthan R, Aubier M, Boczkowski J 2003 Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem 278:27160-27168
Takano K, Al-Mokdad M, Shibata F, Tsuchiya H, Nakagawa H 1999 Rat macrophage inflammatory protein-1alpha, a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo. Inflammation 23:411-424
Takano K, Nakagawa H 2001 Contribution of cytokine-induced neutrophil chemoattractant CINC-2 and CINC-3 to neutrophil recruitment in lipopolysaccharide-induced inflammation in rats. Inflamm Res 50:503-508
Talent JM, Gracy RW 1996 Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for patients with osteoarthritis. Clin Ther 18:1184-1190
Toegel S, Wu SQ, Piana C, Unger FM, Wirth M, Goldring MB, Gabor F, Viernstein H 2008 Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1beta-stimulated C-28/I2 chondrocytes. Osteoarthritis Cartilage 16:1205-1212
Toews GB 1986 Determinants of bacterial clearance from the lower respiratory tract. Semin Respir Infect 1:68-78
Tomida A, Suzuki H, Kim HD, Tsuruo T 1996 Glucose-regulated stresses cause decreased expression of cyclin D1 and hypophosphorylation of retinoblastoma protein in human cancer cells. Oncogene 13:2699-2705
Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G 2005 Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 18:CD002946
Toyoshima H, Hunter T 1994 p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78:67-74
Tsai CY, Lee TS, Kou YR, Wu YL 2009 Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation. J Cell Biochem 108:489-498
Turpeinen T, Nieminen R, Taimi V, Heittola T, Sareila O, Clark AR, Moilanen E, Korhonen R 2011 Dual specificity phosphatase 1 regulates human inducible nitric oxide synthase expression by p38 MAP kinase. Mediators Inflamm 2011:127587
Tyagi A, Agarwal C, Dwyer-Nield LD, Singh RP, Malkinson AM, Agarwal R 2011 Silibinin modulates TNF-alpha and IFN-gamma mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol Carcinog 51:832-842
Ulich TR, Watson LR, Yin SM, Guo KZ, Wang P, Thang H, del Castillo J 1991 The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. Am J Pathol 138:1485-1496
Valvason C, Musacchio E, Pozzuoli A, Ramonda R, Aldegheri R, Punzi L 2008 Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22(Phox) and iNOS expression. Rheumatology (Oxford) 47:31-35
Van Damme J, Proost P, Lenaerts JP, Opdenakker G 1992 Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J Exp Med 176:59-65
van Zoelen MA, Verstege MI, Draing C, de BR, van't VC, Florquin S, Bresser P, van der Zee JS, te Velde AA, von AS, van der PT 2011 Endogenous MCP-1 promotes lung inflammation induced by LPS and LTA. Mol Immunol 48:1468-1476
van der Vliet A, Eiserich JP, Cross CE 2000 Nitric oxide: a pro-inflammatory mediator in lung disease? Respir Res 1:67-72
Wandel S, Juni P, Tendal B, Nuesch E, Villiger PM, Welton NJ, Reichenbach S, Trelle S 2010 Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 341:c4675
Wang W, Nacusi L, Sheaff RJ, Liu X 2005 Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection. Biochemistry 44:14553-14564
Wang Z, Liang R, Huang GS, Piao Y, Zhang YQ, Wang AQ, Dong BX, Feng JL, Yang GR, Guo Y 2006 Glucosamine sulfate-induced apoptosis in chronic myelogenous leukemia K562 cells is associated with translocation of cathepsin D and downregulation of Bcl-xL. Apoptosis 11:1851-1860
Ware LB, Matthay MA 2000 The acute respiratory distress syndrome. N Engl J Med 342:1334-1349
Watanabe K, Konishi K, Fujioka M, Kinoshita S, Nakagawa H 1989 The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein. J Biol Chem 264:19559-19563
Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE 1986 Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis 133:218-225
Wu F, Han M, Wilson JX 2009 Tripterine prevents endothelial barrier dysfunction by inhibiting endogenous peroxynitrite formation. Br J Pharmacol 157:1014-1023
Wu YL, Kou YR, Ou HL, Chien HY, Chuang KH, Liu HH, Lee TS, Tsai CY, Lu ML 2010 Glucosamine regulation of LPS-mediated inflammation in human bronchial epithelial cells. Eur J Pharmacol 635:219-226
Xie QW, Kashiwabara Y, Nathan C 1994 Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem 269:4705-4708
Xing D, Gong K, Feng W, Nozell SE, Chen YF, Chatham JC, Oparil S 2011 O-GlcNAc modification of NFkappaB p65 inhibits TNF-alpha-induced inflammatory mediator expression in rat aortic smooth muscle cells. PLoS One 6:e24021
Xu SQ, El-Deiry WS 2000 p21(WAF1/CIP1) inhibits initiator caspase cleavage by TRAIL death receptor DR4. Biochem Biophys Res Commun 269:179-190
Xu W, Zheng S, Dweik RA, Erzurum SC 2006 Role of epithelial nitric oxide in airway viral infection. Free Radic Biol Med 41:19-28
Yadav A, Saini V, Arora S 2010 MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta 411:1570-1579
Yinnon AM, Butnaru A, Raveh D, Jerassy Z, Rudensky B 1996 Klebsiella bacteraemia: community versus nosocomial infection. QJM 89:933-941
Yomogida S, Hua J, Sakamoto K, Nagaoka I 2008a Glucosamine suppresses interleukin-8 production and ICAM-1 expression by TNF-alpha-stimulated human colonic epithelial HT-29 cells. Int J Mol Med 22:205-211
Yomogida S, Kojima Y, Tsutsumi-Ishii Y, Hua J, Sakamoto K, Nagaoka I 2008b Glucosamine, a naturally occurring amino monosaccharide, suppresses dextran sulfate sodium-induced colitis in rats. Int J Mol Med 22:317-323
Yoshida H, Kwon AH, Kaibori M, Tsuji K, Habara K, Yamada M, Kamiyama Y, Nishizawa M, Ito S, Okumura T 2008 Edaravone prevents iNOS expression by inhibiting its promoter transactivation and mRNA stability in cytokine-stimulated hepatocytes. Nitric Oxide 18:105-112
Yu Z, Zhang W, Kone BC 2002 Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J 367:97-105
Zarkowska T, Mittnacht S 1997 Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases. J Biol Chem 272:12738-12746
Zhang B, Perpetua M, Fulmer M, Harbrecht BG 2004 JNK signaling involved in the effects of cyclic AMP on IL-1beta plus IFNgamma-induced inducible nitric oxide synthase expression in hepatocytes. Cell Signal 16:837-846
Zhang L, Liu WS, Han BQ, Peng YF, Wang DF 2006 Antitumor activities of D-glucosamine and its derivatives. J Zhejiang Univ Sci B 7:608-614
Zhou R, Gong AY, Eischeid AN, Chen XM 2012 miR-27b targets KSRP to coordinate TLR4-mediated epithelial defense against Cryptosporidium parvum infection. PLoS Pathog 8:e1002702
Zlotnik A, Morales J, Hedrick JA 1999 Recent advances in chemokines and chemokine receptors. Crit Rev Immunol 19:1-47