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研究生:詹雅羽
研究生(外文):Ya-Yu Jan
論文名稱:探討第二型趨化激素影響人類冠狀動脈內皮細胞第四型類鐸接受器之表現與機轉
論文名稱(外文):The Mechanisms of Eotaxin-2-induced toll-like receptor 4 expression in human coronary arterial endothelial cells
指導教授:陳建和陳建和引用關係
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學檢驗暨生物技術學系所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:52
中文關鍵詞:第二型趨化激素第四型類鐸接受器動脈粥狀硬化人類冠狀動脈內皮細胞
外文關鍵詞:Eotaxin-2Toll-like receptor 4Human antigen RAtherosclerosisHuman coronary arterial endothelial cell (HCAEC)
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動脈分別是由內中外三層細胞所構成,其中最內層為內皮細胞,其主要功能在調控血管收縮、血液中的免疫細胞作用及細胞激素的產生。當內皮細胞機能失調時,不但改變內皮細胞抗發炎及抗凝固的特性,也降低內皮細胞的生長,將無法維持生理平衡。內皮細胞功能缺損常出現在心血管疾病或發炎性疾病(如高血壓、動脈粥狀硬化、糖尿病、過敏性疾病)的病人當中。
動脈粥狀硬化就是動脈內皮細胞的一種發炎性病變,原因可能為高血脂、高血糖、高同半胱胺酸血症或是病毒細菌感染…等引發血管內皮通透性增加,低密度膽固醇因為體積小得以滲入動脈血管壁內膜堆積,聚積於動脈內膜的低密度脂蛋白膽固醇與蛋白多醣結合後,容易被氧化並釋出磷脂質,進而激活覆蓋在表層的細胞,導致內皮細胞增加表面附著器的表現,其後釋出化學物質,吸引單核球及淋巴球進入內膜區,蛻變為巨噬細胞。大量的巨噬細胞吞噬低密度脂蛋白膽固醇顆粒形成脂肪斑紋,之後惡化成脂肪斑塊。類鐸接受器是哺乳類免疫系統中相當重要的接受器,它們主要的功能是去偵測外來病原菌的入侵。一但偵測到有病原菌的入侵,類鐸接受器會啟動訊息傳導活化先天性免疫反應 (innate immunity),進而影響到後續的後天性反應反應(adaptive immunity)。第四型類鐸接受器是脂多醣(lipopolysaccharide;LPS)在內皮細胞上的主要接受器,當細胞受到脂多醣刺激後,藉由血管內皮細胞表現黏著分子(如ICAM-1及VCAM-1),促使循環中的白血球黏著到血管壁上,進一步移行到發炎組織部位,執行免疫反應。除此之外有許多內生性的慢性發炎分子也能與第四型類鐸接受器結合,引發免疫反應。
本研究所使用的刺激物第二型趨化激素就是一種慢性發炎物質,為趨化嗜酸性白血球的重要因子,是由73個胺基酸所組成的蛋白,可誘導嗜酸性白血球來聚集、活化並加強其與血管內皮細胞之附著能力。第二型趨化激素主要是由嗜酸性白血球所分泌,產生過敏現象時往往能在血中偵測到高量的第二型趨化激素濃度。內皮細胞的發炎也和其有相關性,許多動脈粥狀硬化的病人,因為免疫系統受到影響,所以較正常人容易感染發炎,臨床偵測體內各項細胞激素濃度發現,第二型趨化激素的量明顯較正常人高。
為了進一步瞭解過敏反應與動脈粥狀硬化發炎反應的相關性,不同於以往傳統實驗利用脂多醣刺激細胞來看激素的分泌情形,我們反過來利用利用第二型趨化激素來刺激人類冠狀動脈內皮細胞,來看其內皮細胞表現第四型類鐸接受器的表現與機轉。
首先確認人類冠狀動脈內皮細胞上有第二型趨化激素的接受器CCR3,之後再確認所加的第二型趨化激素劑量不會造成細胞死亡。從RT-PCR實驗結果發現,第四型類鐸接受器mRNA的表現量會因為第二型趨化激素的刺激而增加。過去許多研究都認為基因的調控是透過DNA或是蛋白質的層面來影響,但近年來發現許多基因是透過RNA的層級來影響調控,所以後轉錄修飾(post-transcriptional modification)的概念漸漸被提出,後轉錄修飾的調控涉及兩個層面,分別是轉錄的效益(translational efficiency)以及mRNA的穩定度(mRNA stability)。針對後轉錄修飾的調控,我們發現利用第二型趨化激素刺激後RNA 結合蛋白HuR會結合在第四型類鐸接受器3’UTR 來增加其mRNA的穩定度。蛋白層面利用西方墨點法來證實經過第二型趨化激素刺激後會透過MAPK 路徑來調控第四型類鐸接受器蛋白表現量的增加。最後是看蛋白運輸的部分,利用第二型趨化激素刺激內皮細胞後由西方墨點法結果可以發現運輸第四型類鐸接受器到膜上的PRAT4A及GRP9蛋白表現量亦會增加。


Objective: Eotaxin-2 interacts with toll-like receptor 4 (TLR4) and induces inflammatory responses in human coronary arterial endothelial cells (HCAECs), which plays an important role in atherogenesis. The objective of this study was to investigate the mechanisms involving eotaxin-2-induced TLR4 expression in HCAECs.

Methods and results: Stimulation via eotaxin-2 significantly increased TLR4 mRNA level in HCAECs by real time polymerase chain reaction
(RT-PCR). In addition, on eotaxin-2 treatment also increased TLR4 protein expression. An actinomycin D chase experiment showed that eotaxin-2 increased the stability and half life of TLR4 mRNA. Immunocytofluoresence data showed that after treated HCAECs with eotaxin-2, human antigen R (HuR) translocated from nucleus to cytoplasm. Eotaxin-2 induced 3’UTR of TLR4 mRNA-containing luciferase plasmid expression in HCAECs. These results showed that the HuR modultes 3’untranslated region (3’UTR)-mediated gene expression. On the other hand, RT-PCR demonstrated that eotaxin-2-induced TLR4 mRNA expression was reduced by SB203580 (a p38 MAPK inhibitor) or PD98059 (an ERK1/2 inhibitor) , but not by SP600125 (an SAPK/JNK inhibitor). However, eotaxin-2-induced TLR4 protein expression was reduced by SB203580 or SP600125, but not by PD98059.

Conclusion: Activation of HuR and the mitogen-activated protein kinase(MAPK)-signaling pathways contribute to eotaxin-2-induce TLR4 mRNA and protein expression in HCAECs.


Abstract………………………………………………………………………………………………………1~4
Abbreviation……………………………………………………………………………………………5~6
1. Introduction……………………………………………………………………………………………7~13
1.1 Atherosclerosis…………………………………………………………………………7~9
1.2 Toll-like receptors………………………………………………………………9~11
1.3 Eotaxin-2…………………………………………………………………………………………11
1.4 mRNA binding protein……………………………………………………………12~13
2. Materials and Methods……………………………………………………………………14~18
2.1 Cell culture…………………………………………………………………………………14
2.2 MTT assay…………………………………………………………………………………………14
2.3 Actinomycin D Chase Experiments………………………………14
2.4 RNA extraction……………………………………………………………………………15
2.5 Quantitative Real Time Polymerase Chain
Reaction……………………………………………………………………………………………15
2.6 Western blotting………………………………………………………………………15~16
2.7 Immunocytochemical staining…………………………………………16
2.8 Transfection and luciferase reporter
assay……………………………………………………………………………………………………16~17
2.9 Statistical Analyses……………………………………………………………17
3. Results…………………………………………………………………………………………………………19~23
4. Discussion…………………………………………………………………………………………………24~27
5. References…………………………………………………………………………………………………28~34
6. Figures…………………………………………………………………………………………………………35~51
Fig. 1……………………………………………………………………………………………………………35
Fig. 2……………………………………………………………………………………………………………35
Fig. 3……………………………………………………………………………………………………………36~37
Fig. 4……………………………………………………………………………………………………………38~39
Fig. 5……………………………………………………………………………………………………………40
Fig. 6……………………………………………………………………………………………………………41~46
Fig. 7……………………………………………………………………………………………………………47~48
Fig. 8……………………………………………………………………………………………………………49~50
Fig. 9……………………………………………………………………………………………………………51
Tab. 1……………………………………………………………………………………………………………52


1.Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-1143
2.Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G, et al. Plasma homocysteine as a risk factor for vascular disease. The european concerted action project. JAMA : the journal of the American Medical Association. 1997;277:1775-1781
3.Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109:III27-32
4.Nozue T, Michishita I, Ishibashi Y, Ito S, Iwaki T, Mizuguchi I, Miura M, Ito Y, Hirano T. Small dense low-density lipoprotein cholesterol is a useful marker of metabolic syndrome in patients with coronary artery disease. Journal of atherosclerosis and thrombosis. 2007;14:202-207
5.Crawford DW, Blankenhorn DH. Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis. 1991;89:97-108
6.Gleissner CA, Leitinger N, Ley K. Effects of native and modified low-density lipoproteins on monocyte recruitment in atherosclerosis. Hypertension. 2007;50:276-283
7.Llorente-Cortes V, Badimon L. Ldl receptor-related protein and the vascular wall: Implications for atherothrombosis. Arteriosclerosis, thrombosis, and vascular biology. 2005;25:497-504
8.Galkina E, Ley K. Leukocyte influx in atherosclerosis. Current drug targets. 2007;8:1239-1248
9.Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially l-selectin dependent. The Journal of experimental medicine. 2006;203:1273-1282
10.Khoo JC, Miller E, McLoughlin P, Steinberg D. Enhanced macrophage uptake of low density lipoprotein after self-aggregation. Arteriosclerosis. 1988;8:348-358
11.Lusis AJ. Atherosclerosis. Nature. 2000;407:233-241
12.Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circulation research. 2000;87:840-844
13.Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109:159-165
14.Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial dysfunction in diabetes: The role of reparatory mechanisms. Diabetes care. 2011;34 Suppl 2:S285-290
15.Wanner A, Mendes ES. Airway endothelial dysfunction in asthma and chronic obstructive pulmonary disease: A challenge for future research. American journal of respiratory and critical care medicine. 2010;182:1344-1351
16.Pober J, Cotran RS. What can be learned from the expression of endothelial adhesion molecules in tissues? Laboratory investigation; a journal of technical methods and pathology. 1991;64:301-305
17.Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of c-reactive protein on human endothelial cells. Circulation. 2000;102:2165-2168
18.Sawa Y, Ueki T, Hata M, Iwasawa K, Tsuruga E, Kojima H, Ishikawa H, Yoshida S. Lps-induced il-6, il-8, vcam-1, and icam-1 expression in human lymphatic endothelium. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2008;56:97-109
19.Watson C, Whittaker S, Smith N, Vora AJ, Dumonde DC, Brown KA. Il-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes. Clinical and experimental immunology. 1996;105:112-119
20.Poston RN, Haskard DO, Coucher JR, Gall NP, Johnson-Tidey RR. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. The American journal of pathology. 1992;140:665-673
21.Cybulsky MI, Gimbrone MA, Jr. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991;251:788-791
22.Rao RM, Yang L, Garcia-Cardena G, Luscinskas FW. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circulation research. 2007;101:234-247
23.Qiu P, Pan PC, Govind S. A role for the drosophila toll/cactus pathway in larval hematopoiesis. Development. 1998;125:1909-1920
24.Chtarbanova S, Imler JL. Microbial sensing by toll receptors: A historical perspective. Arteriosclerosis, thrombosis, and vascular biology. 2011;31:1734-1738
25.Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr. A human homologue of the drosophila toll protein signals activation of adaptive immunity. Nature. 1997;388:394-397
26.Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S. A toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303:1522-1526
27.Takeda K, Akira S. Toll-like receptors in innate immunity. International immunology. 2005;17:1-14
28.Gay NJ, Gangloff M. Structure and function of toll receptors and their ligands. Annual review of biochemistry. 2007;76:141-165
29.Botos I, Segal DM, Davies DR. The structural biology of toll-like receptors. Structure. 2011;19:447-459
30.O''Neill LA, Bowie AG. The family of five: Tir-domain-containing adaptors in toll-like receptor signalling. Nature reviews. Immunology. 2007;7:353-364
31.Akashi S, Saitoh S, Wakabayashi Y, Kikuchi T, Takamura N, Nagai Y, Kusumoto Y, Fukase K, Kusumoto S, Adachi Y, Kosugi A, Miyake K. Lipopolysaccharide interaction with cell surface toll-like receptor 4-md-2: Higher affinity than that with md-2 or cd14. The Journal of experimental medicine. 2003;198:1035-1042
32.Erridge C, Bennett-Guerrero E, Poxton IR. Structure and function of lipopolysaccharides. Microbes and infection / Institut Pasteur. 2002;4:837-851
33.Visintin A, Mazzoni A, Spitzer JA, Segal DM. Secreted md-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to toll-like receptor 4. Proceedings of the National Academy of Sciences of the United States of America. 2001;98:12156-12161
34.Golias C, Tsoutsi E, Matziridis A, Makridis P, Batistatou A, Charalabopoulos K. Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease. In Vivo. 2007;21:757-769
35.Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O. Molecular cloning of human eotaxin, an eosinophil-selective cc chemokine, and identification of a specific eosinophil eotaxin receptor, cc chemokine receptor 3. The Journal of biological chemistry. 1996;271:7725-7730
36.Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. The Journal of experimental medicine. 1996;183:2349-2354
37.Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. The Journal of experimental medicine. 1996;183:2437-2448
38.Menzies-Gow A, Robinson DS. Eosinophil chemokines and their receptors: An attractive target in asthma? Lancet. 2000;355:1741-1743
39.Rankin SM, Conroy DM, Williams TJ. Eotaxin and eosinophil recruitment: Implications for human disease. Molecular medicine today. 2000;6:20-27
40.Humbles AA, Conroy DM, Marleau S, Rankin SM, Palframan RT, Proudfoot AE, Wells TN, Li D, Jeffery PK, Griffiths-Johnson DA, Williams TJ, Jose PJ. Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: Analysis in a guinea pig model in vivo. The Journal of experimental medicine. 1997;186:601-612
41.Forssmann U, Uguccioni M, Loetscher P, Dahinden CA, Langen H, Thelen M, Baggiolini M. Eotaxin-2, a novel cc chemokine that is selective for the chemokine receptor ccr3, and acts like eotaxin on human eosinophil and basophil leukocytes. The Journal of experimental medicine. 1997;185:2171-2176
42.Min JW, Lee JH, Park CS, Chang HS, Rhim TY, Park SW, Jang AS, Shin HD. Association of eotaxin-2 gene polymorphisms with plasma eotaxin-2 concentration. Journal of human genetics. 2005;50:118-123
43.Elsner J, Petering H, Kluthe C, Kimmig D, Smolarski R, Ponath P, Kapp A. Eotaxin-2 activates chemotaxis-related events and release of reactive oxygen species via pertussis toxin-sensitive g proteins in human eosinophils. European journal of immunology. 1998;28:2152-2158
44.Hansson GK. Immune mechanisms in atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2001;21:1876-1890
45.Kracht M, Saklatvala J. Transcriptional and post-transcriptional control of gene expression in inflammation. Cytokine. 2002;20:91-106
46.Zubiaga AM, Belasco JG, Greenberg ME. The nonamer uuauuuauu is the key au-rich sequence motif that mediates mrna degradation. Molecular and cellular biology. 1995;15:2219-2230
47.Bakheet T, Frevel M, Williams BR, Greer W, Khabar KS. Ared: Human au-rich element-containing mrna database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic acids research. 2001;29:246-254
48.Yoon JH, Abdelmohsen K, Gorospe M. Posttranscriptional gene regulation by long noncoding rna. Journal of molecular biology. 2013;425:3723-3730
49.Hinman MN, Lou H. Diverse molecular functions of hu proteins. Cellular and molecular life sciences : CMLS. 2008;65:3168-3181
50.Peng SS, Chen CY, Xu N, Shyu AB. Rna stabilization by the au-rich element binding protein, hur, an elav protein. The EMBO journal. 1998;17:3461-3470
51.Myer VE, Fan XC, Steitz JA. Identification of hur as a protein implicated in auuua-mediated mrna decay. The EMBO journal. 1997;16:2130-2139
52.Wang W, Caldwell MC, Lin S, Furneaux H, Gorospe M. Hur regulates cyclin a and cyclin b1 mrna stability during cell proliferation. The EMBO journal. 2000;19:2340-2350
53.Guo X, Hartley RS. Hur contributes to cyclin e1 deregulation in mcf-7 breast cancer cells. Cancer research. 2006;66:7948-7956
54.Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M. Concurrent versus individual binding of hur and auf1 to common labile target mrnas. The EMBO journal. 2004;23:3092-3102
55.Wang W, Furneaux H, Cheng H, Caldwell MC, Hutter D, Liu Y, Holbrook N, Gorospe M. Hur regulates p21 mrna stabilization by uv light. Molecular and cellular biology. 2000;20:760-769
56.Dean JL, Wait R, Mahtani KR, Sully G, Clark AR, Saklatvala J. The 3'' untranslated region of tumor necrosis factor alpha mrna is a target of the mrna-stabilizing factor hur. Molecular and cellular biology. 2001;21:721-730
57.Srikantan S, Gorospe M. Hur function in disease. Front Biosci (Landmark Ed). 2012;17:189-205
58.Xu N, Chen CY, Shyu AB. Versatile role for hnrnp d isoforms in the differential regulation of cytoplasmic mrna turnover. Molecular and cellular biology. 2001;21:6960-6971
59.Sarkar B, Lu JY, Schneider RJ. Nuclear import and export functions in the different isoforms of the auf1/heterogeneous nuclear ribonucleoprotein protein family. The Journal of biological chemistry. 2003;278:20700-20707
60.Gratacos FM, Brewer G. The role of auf1 in regulated mrna decay. Wiley interdisciplinary reviews. RNA. 2010;1:457-473
61.Wilson GM, Sutphen K, Chuang K, Brewer G. Folding of a+u-rich rna elements modulates auf1 binding. Potential roles in regulation of mrna turnover. The Journal of biological chemistry. 2001;276:8695-8704
62.Sirenko O, Bocker U, Morris JS, Haskill JS, Watson JM. Il-1 beta transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mrna degradation factors. Immunology and cell biology. 2002;80:328-339
63.Lafon I, Carballes F, Brewer G, Poiret M, Morello D. Developmental expression of auf1 and hur, two c-myc mrna binding proteins. Oncogene. 1998;16:3413-3421
64.Shyu AB, Belasco JG, Greenberg ME. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mrna decay. Genes & development. 1991;5:221-231
65.Nakamaki T, Imamura J, Brewer G, Tsuruoka N, Koeffler HP. Characterization of adenosine-uridine-rich rna binding factors. Journal of cellular physiology. 1995;165:484-492
66.Fellows A, Griffin ME, Petrella BL, Zhong L, Parvin-Nejad FP, Fava R, Morganelli P, Robey RB, Nichols RC. Auf1/hnrnp d represses expression of vegf in macrophages. Molecular biology of the cell. 2012;23:1414-1422
67.Guo X, Gourronc F, Audic Y, Lyons-Levy G, Mitchell T, Hartley RS. Elra and auf1 differentially bind cyclin b2 mrna. Biochemical and biophysical research communications. 2008;377:653-657
68.Lin S, Wang W, Wilson GM, Yang X, Brewer G, Holbrook NJ, Gorospe M. Down-regulation of cyclin d1 expression by prostaglandin a(2) is mediated by enhanced cyclin d1 mrna turnover. Molecular and cellular biology. 2000;20:7903-7913
69.Mazan-Mamczarz K, Kuwano Y, Zhan M, White EJ, Martindale JL, Lal A, Gorospe M. Identification of a signature motif in target mrnas of rna-binding protein auf1. Nucleic acids research. 2009;37:204-214
70.Amann BT, Worthington MT, Berg JM. A cys3his zinc-binding domain from nup475/tristetraprolin: A novel fold with a disklike structure. Biochemistry. 2003;42:217-221
71.Lagnado CA, Brown CY, Goodall GJ. Auuua is not sufficient to promote poly(a) shortening and degradation of an mrna: The functional sequence within au-rich elements may be uuauuua(u/a)(u/a). Molecular and cellular biology. 1994;14:7984-7995
72.Kotlyarov A, Neininger A, Schubert C, Eckert R, Birchmeier C, Volk HD, Gaestel M. Mapkap kinase 2 is essential for lps-induced tnf-alpha biosynthesis. Nature cell biology. 1999;1:94-97
73.Necela BM, Cidlowski JA. Mechanisms of glucocorticoid receptor action in noninflammatory and inflammatory cells. Proceedings of the American Thoracic Society. 2004;1:239-246
74.Raineri I, Wegmueller D, Gross B, Certa U, Moroni C. Roles of auf1 isoforms, hur and brf1 in are-dependent mrna turnover studied by rna interference. Nucleic acids research. 2004;32:1279-1288
75.Mahtani KR, Brook M, Dean JL, Sully G, Saklatvala J, Clark AR. Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mrna stability. Molecular and cellular biology. 2001;21:6461-6469
76.Korhonen R, Linker K, Pautz A, Forstermann U, Moilanen E, Kleinert H. Post-transcriptional regulation of human inducible nitric-oxide synthase expression by the jun n-terminal kinase. Molecular pharmacology. 2007;71:1427-1434
77.Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrancois L, Li Z. Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity. 2007;26:215-226
78.Takahashi K, Shibata T, Akashi-Takamura S, Kiyokawa T, Wakabayashi Y, Tanimura N, Kobayashi T, Matsumoto F, Fukui R, Kouro T, Nagai Y, Takatsu K, Saitoh S, Miyake K. A protein associated with toll-like receptor (tlr) 4 (prat4a) is required for tlr-dependent immune responses. The Journal of experimental medicine. 2007;204:2963-2976



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