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研究生(外文):Hsin-Yu Yeh
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(外文):Sai-Koong Tan
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.
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