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研究生:葉欣裕
研究生(外文):Hsin-Yu Yeh
論文名稱:脂多醣誘發似腦下垂體濾泡星狀細胞TtT/GF之發炎變化與訊息傳導途徑之研究
論文名稱(外文):Study on LPS-induced inflammatory reaction and signaling pathway in pituitary folliculo-stellate like Cell, TtT/GF
指導教授:陳賽君陳賽君引用關係
指導教授(外文):Sai-Koong Tan
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學生物技術研究所
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:2004
畢業學年度:92
語文別:中文
論文頁數:83
中文關鍵詞:脂多醣體濾泡星狀細胞混合培養腦下垂體前葉CXC趨化激素巨噬細胞發炎蛋白-2
外文關鍵詞:LPSfolliculo-stellate cellTtT/GFMIP-2p38PI3 kinase
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腦下垂體位於血腦屏障之外區域,感染時可直接受細菌脂多醣體(Lipopolysaccharide,LPS)之影響。濾泡星狀細胞(folliculo-stellate cell,FS cell)是在腦下垂體前葉已知不分泌荷爾蒙的細胞,可調節及支持其他荷爾蒙分泌細胞之生長與荷爾蒙分泌,其於發炎時所扮演的角色至今仍不十分明確。我們利用似濾泡星狀細胞TtT/GF細胞為模式,主要鑑定TtT/GF細胞是否與具一般吞噬細胞相似之特性。結果發現TtT/GF具有scavenger receptor A,會表現TLR-4、CD14、MD2,且於10 ng/ml LPS作用短時間(3 hr)即引發IL-1β、IL-6、TNF-α等發炎前細胞激素基因表現,但會抑制TGF-beta 1之基因表現;chemokine MIP-2也會受LPS誘發。而LPS會改變表現TLR-4、CD14 mRNA表現量。
TtT/GF細胞scavenger receptor A表現不受LPS作用時間有所改變, LPS作用也能提高細胞之吞噬能力。有趣的是TtT/GF細胞不像巨噬細胞,並不受到LPS誘發產生大量之ROS(Reactive oxygen species);故推測LPS雖能於TtT/GF引起與巨噬細胞相似之細胞效應,但其機制有所不同,可能不經NO。
為進一步探討LPS之作用機制,我們選用參與TtT/GF移動能力相關之MIP-2為目標,利用訊息傳導途徑抑制劑SB203580或LY294002,結果顯示此二抑制劑能抑制MIP-2基因表現與細胞移動,p38和PI3 kinase pathway參與LPS誘發之MIP-2基因與細胞移動。
為觀察FS細胞對荷爾蒙分泌細胞之影響,利用TtT/GF與GH3細胞混合培養模式,發現TtT/GF在無LPS作用下即可抑制GH3細胞PRL mRNA,LPS可刺激GH3細胞PRL基因表現;而LPS作用下TtT/GF仍可抑制PRL基因表現。綜合以上結果,腦下垂體FS細胞於發炎時可以扮演吞噬細胞之角色,且能抑制PRL基因表現。
Bacterial lipopolysaccharide (LPS), the major structural component of the outer wall of Gram-negative bacterial, is a potent activator of macrophages. Pituitary folliculo-stellate (FS) cells are nonhormonal secreting cells of anterior pituitary gland, whose function remain poorly defined. The aim of this study is to ask whether pituitary FS cell is a macrophage-like cell. By using a murine pituitary folliculo-stellate like cell line, TtT/GF, we demonstrated that TtT/GF expresses scavenger receptor A and two components of the LPS receptor complex, such as Toll-like receptor, MD-2 and CD14. LPS alters the expression of both TLR-4 and CD14, but not scavenger receptor. After administration of LPS, TtT/GF highly expresses proinflammatory cytokines TNF-α, IL-1β, IL-6, TGF-β1 and chemokine MIP-2, but the production of nitric oxide and reactive oxygen species were not observed. On the other hand, both the mobility and phagocytosis of TtT/GF are enhanced by LPS. LPS induced phosphorylation of MAPK pathway (p38, JNK, ERK) and Akt kinases. Both inhibitor of p38 (SB203580) and PI3-kinase (LY294002) inhibited LPS-induced MIP-2 gene expression and the mobility of the cell, but not the ERK inhibitor (PD98059) and JNK inhibitor (SP600125), suggesting effect of LPS on mobility via p38 and PI3 kinase pathway. We found that TtT/GF down regulated PRL mRNA expression in GH3 cells at both vehicle and LPS treated condition. Taken together, TtT/GF may play as a macrophage-like cells during inflammation and regulate PRL gene expression in anterior pituitary gland.
Allaerts W, Carmeliet P, Denef C. 1990. New perspectives in the function of pituitary folliculo-stellate cells. Mol Cell Endocrinol 71(2):73-81.
Andersen B, Rosenfeld MG. 1994. Pit-1 determines cell types during development of the anterior pituitary gland. A model for transcriptional regulation of cell phenotypes in mammalian organogenesis. J Biol Chem 269(47):29335-8.
Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, Strieter RM. 2000. CXC chemokines in angiogenesis. J Leukoc Biol 68(1):1-8.
Beutler B. 2004. Innate immunity: an overview. Mol Immunol 40(12):845-59.
Bozic CR, Gerard NP, von Uexkull-Guldenband C, Kolakowski LF Jr, Conklyn MJ, Breslow R, Showell HJ, Gerard C. 1994. The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. J Biol Chem 269(47):29355-8.
Chrousos GP. 1995. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351-62.
Cocchia D, Miani N. 1980. Immunocytochemical localization of the brain-specific S-100 protein in the pituitary gland of adult rat. J Neurocytol 9:771-782.
Cohen J. 2002. The immunopathogenesis of sepsis. Nature 420:885-891
Driscoll KE. 1994. Macrophage inflammatory proteins: biology and role in pulmonary inflammation. Exp Lung Res 20(6):473-90.
Fan J, Malik AB. 2003. Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors. Nat Med 9(4):477.
Farquhar MG. 1957. ”Corticotrophs’’ of the rat adenohypoysis as revealed by electron microscopy. Anat Rec 127:291.
Faure E, Thomas L, Xu H, Medvedev A, Equils O, Arditi M. 2001. Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. J Immunol 166(3):2018-24.
Ferrara N, Henzel WJ. 1989. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161(2):851-8.
Feuillet-Fieux MN, Golub RM, Nguyen AT, Zamfirescu P, Descamps-Latscha B. 1984. Effect of LPS on the oxidative metabolism of peritoneal and spleen cells from LPS sensitive and resistant mice. J Clin Lab Immunol 15(3):155-61.
Forman HJ, Torres M. 2001. Redox signaling in macrophages. Mol Aspects Med 22(4-5):189-216.
Frederick MJ, Clayman GL. 2001. Chemokines in cancer. Expert Rev Mol Med 3:1-18.
Frevert CW, Farone A, Danaee H, Paulauskis JD, Kobzik L. 1995. Functional characterization of rat chemokine macrophage inflammatory protein-2. Inflammation. 19(1):133-42.
Fujihara M, Connolly N, Ito N and Suzuki T. 1994. Properties of pretein kinase C isoforms (βII,ε,andζ)in a macrophage cell line (J744) and their role in LPS-induced nitric oxide production. J Immunnol 152:1898-1906.
Fujihara M, Muroi M, Muroi Y, Ito N. Suzuki T. 1993. Mechanism of lipopolysaccharide-triggered junB activation in mouse macrophage-like cell line (J744). J Biol Chem 268:14898-14905.
Fujihara M, Muroi M, Tanamoto K, Suzuki T, Azuma H and Ikeda H. 2003. Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: roles of the receptor complex. Pharmacology &therapeutics 100:171-194.
Giometto B, Miotto D, Botteri M, Alessio L, Scanarini M, An SF, Tavolato B. 1997. Folliculo-stellate cells of human pituitary adenomas: immunohistochemical study of the monocyte/macrophage phenotype expression. Neuroendocrinology 65(1):47-52.
Gloddek J, Lohrer P, Stalla J, Arzt E, Stalla GK, Renner U. 2001. The intrapituitary stimulatory effect of lipopolysaccharide on ACTH secretion is mediated by paracrine-acting IL-6. Exp Clin Endocrinol Diabetes 109(8):410-5.
Herrera-Velit P, Reiner NE. 1996. Bacterial lipopolysaccharideinduces the association and coordinate activation of p53/56lyn and phosphatidylinositol 3-kinase in human monocytes. J Immunnol 156:1157-1165.
Inoue K, Couch EF, Takano K, Ogawa S. 1999. The structure and function of folliculo-stellate cells in the anterior pituitary gland, Arch Histol Cytol 62:205–218.
Inoue K, Matsumoto H, Koyama C, Shibata K, Nakazato Y, Ito A. 1992. Establishment of a folliculo-stellate-loke cell line from a murine thyrotropic pituitary tumor. Endocrinology 131:3110–3116.
Jakway JP, Defrance AL. 1986. pertussis toxin inhibition of B cell and macrophage responses to Bacterial lipopolysaccharideinduces. Science 234:743-746.
Jarrar D, Kuebler JF, Rue LW 3rd, Matalon S, Wang P, Bland KI, Chaudry IH. 2002. Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms. Am J Physiol Lung Cell Mol Physiol 283(4):L799-805.
Jiang Q, Akashi S, Miyake K, Petty HR. 2000. Cutting Edge: Lipopolysaccharide induces physical proximity between CD14 and Toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-κB. J Immunol 165:3541–44.
Kim DS, Han JH, Kwon HJ. 2003. NF-kappaB and c-Jun-dependent regulation of macrophage inflammatory protein-2 gene expression in response to lipopolysaccharide in RAW 264.7 cells. Mol Immunol 40(9):633-43.
Kobayashi H, Fukata J, Murakami N, Usui T, Ebisui O, Muro S, Hanaoka I, Inoue K, Imura H, Nakao K. 1997. Tumor necrosis factor receptors in the pituitary cells. Brain Res 758(1-2):45-50.
Kobayashi H, Fukata J, Murakami N, Usui T, Ebisui O, Muro S, Hanaoka I, Inoue K, Imura H, Nakao K. 1997. Tumor necrosis factor receptors in the pituitary cells. Brain Res 758(1-2):45-50.
Koike K, Zhang ZX, Sakamoto Y, Kanda Y, Murakami K, Miyake A, Inoue M. 1997. The pituitary folliculo-stellate cell line TtT/GF augments basal and TRH-induced prolactin secretion by GH3 cell. Life Sci 61(25):2491-7.
Ling W, Lougheed M, Suzuki H, Buchan A, Kodama T, Steinbrecher UP. 1997. Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene. J Clin Invest 100(2):244-52.
Lohrer P, Gloddek J, Nagashima AC, Korali Z, Hopfner U, Pereda MP, Arzt E, Stalla GK, Renner U. 2000. Lipopolysaccharide directly stimulates the intrapituitary interleukin-6 production by folliculostellate cells via specific receptors and the p38alpha mitogen-activated protein kinase/nuclear factor-kappaB pathway. Endocrinology 141(12):4457-65.
McCann SM, Antunes-Rodrigues J, Franci CR, Anselmo-Franci JA, Karanth S, Rettori V. 2000. Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection. Braz J Med Biol Res 33(10):1121-31.
McCann SM, Licinio J, Wong ML, Yu WH, Karanth S, Rettorri V. 1998. The nitric oxide hypothesis of aging. Exp Gerontol 33(7-8):813-26.
McCann SM. 1997. The nitric oxide hypothesis of brain aging. Exp Gerontol 32(4-5):431-40.
Medzhitov R, Janeway C Jr. 2003. Innate immune recognition: mechanisms and pathways. Immuno Rev 173:89-97.
Mogi C, Miyai S, Nishimura Y, Fukuro H, Yokoyama K, Takaki A, and Inoue K. 2004. Differentiation of skeletal muscle from pituitary folliculo-stellate cells and endocrine progenitor cells. Exp Cell Res 292:288– 294.
Moore KJ, Freeman MW, Reed GL. 2000. Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: a divergent response relative to human THP-1 monocyte/macrophages. J Immunol 164(5):2692-700.
Morand I, Fonlupt P, Guerrier A, Trouillas J, Calle A, Remy C, Rousset B, Munari-Silem Y. 1996. Cell-to-cell communication in the anterior pituitary: evidence for gap junction-mediated exchanges between endocrine cells and folliculostellate cells. Endocrinology 137(8):3356-67.
Murali K, Rao K. 2001. MAP kinase activation in macrophages. J Leukoc Biol 69: 3–10.
Muroi M, Suzuki T. 1993. Role of protein kinase A in LPS-induced activaction of NF-κB protein of a mouse macrophage-like cell line, J744A. Cell Signal 5:289-298.
Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, et al. 2002. Essential role of MD-2in LPS responsiveness and TLR4 distribution. Nat Immunol 3:667–72.
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):545-50.
Nakajima T, Yamaguchi H, Takahashi K. 1980. S-100 protein in folliculo-stellate cells of the rat pituitary anterior lobe. Brain Res 191:523–531.
Nick JA, Young SK, Brown KK, Avdi NJ, Arndt PG, Suratt BT, Janes MS, Henson PM, Worthen GS. 2000. Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol 164(4):2151-9.
Nickoloff BJ, Mitra RS, Varani J, Dixit VM, Polverini PJ. 1994. Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis. Am J Pathol 144:820–28.
Ojaniemi M, Glumoff V, Harju K, Liljeroos M, Vuori K, Hallman M. 2003. Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages. Eur J Immunol 33(3):597-605.
Platt N, Gordon S. 2001. Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale. Clin Invest 108(5):649-54.
Raetz CRH. 1990 Biochemistry of endotoxins. Annu Rev Biochem 59:129–170.
Renner U, Gloddek J, Pereda MP, Arzt E, Stalla GK. 1998. Regulation and role of intrapituitary IL-6 production by folliculostellate cells. Domest Anim Endocrinol 15(5):353-62.
Renner U, Lohrer P, Schaaf L, Feirer M, Schmitt K, Onofri C, Arzt E, Stalla GK. 2002. Transforming growth factor-beta stimulates vascular endothelial growth factor production by folliculostellate pituitary cells. Endocrinology 143(10):3759-65.
Rinehart JF, Farquhar MG. 1953. Electrone microscopic studies of the anterior pituitary gland. J Histochem Cytochem 1:93–113.
Rossi D, Zlotnik A. 2000. The biology of chemokines and their receptors. Annu Rev Immunol 18:217-242.
Schiff DE, Kline L, Soldau K, Lee JD, Pugin J, Tobias PS, Ulevitch RJ. 1997. Phagocytosis of gram-negative bacteria by a unique CD14-dependent mechanism. J Leukocyte Biol 62:786.
Stokreef JC, Reifel CW, Shin SH. 1986. A possible phagocytic role for folliculo-stellate cells of anterior pituitary following estrogen withdrawal from primed male rats. Cell Tissue Res 243:255-261.
Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynshi O, Wada Y, Honda M, Kurihara H, Aburatani H, Doi T, Matsumoto A, Azuma S, Noda T, Toyoda Y, Itakura H, Yazaki Y, Kodama T, et al. 1997. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386(6622):292-6.
Tekamp-Olson P, Gallegos C, Bauer D, McClain J, Sherry B, Fabre M, van Deventer S, Cerami A. 1990. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med 172(3):911-9.
Tierney T, Christian HC, Morris JF, Solito E, Buckingham JC. 2003. Evidence from studies on co-cultures of TtT/GF and AtT20 cells that Annexin 1 acts as a paracrine or juxtacrine mediator of the early inhibitory effects of glucocorticoids on ACTH release. J Neuroendocrinol 15(12):1134-43.
Underhill DM, Ozinsky A. 2002. Phagocytosis of microbes: complexity in action. Annu Rev Immunol 20:825-52.
Velasco ME, Roessmann U, Gambetti P. 1982. The presence of glial fibrillary acidic protein in the human pituitary gland. J Neuropathol Exp Neurol 41(2):150-63.
Voss JW, Rosenfeld MG. 1992. Anterior pituitary development: short tales from dwarf mice. Cell 70:527-530.
Walz A, Schmutz P, Mueller C, Schnyder-Candrian S. 1997. Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease. J Leukoc Biol 62:604–11.
Wolpe S.D, Sherry B, Juers D, Davatelis G, Yurt RW A. 1989. Cerami, Identi¢cation and characterization of macrophage in£ammatory protein 2. Proc Natl Acad Sci USA 86:612-616.
Yeh WC, Chen NJ. 2003 Immunology: another toll road. Nature 424(6950):736-7.
Yoshimura S., Osamura R. Y. 1999. Expression of Ptx1 in the adult rat pituitary glands and pituitary cell lines: hormone-secreting cells and folliculo-stellate cells. Cell Tissue Res 298:55–61.
Zhang ZX, Koike K, Sakamoto Y, Jikihara H, Kanda Y, Inoue K, Hirota K, Miyake A. 1997. Pituitary folliculo-stellate-like cell line produces a cytokine-induced neutrophil chemoattractant. Neuropeptides 31(1):46-51.
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