- 作者: Hsuan-Shu Lee Luo-Hwa Miau Chien-Hung Chen Ling-Ling Chiou Guan-Tarn Huang Pei-Ming Yang Jin-Chduan Sheu
- 作者服務機構: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, College of Mediceine, and Liver Disease Prevention and Treatment Rescrch Foundation, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Interleukin一1(IL-1)has been implicated in the regulationof the expression of various matrix metalloproteinases(MMPs) in many mesenchymal celI types, but its role inliver myofibroblasts(MFs) has not been elucidated.Amyofibroblast-like cell line, MG2,was derived from anisolate of rat hepatic stellate cells(HSCs).These cellsexpressed desmin,vimentin,smooth muscle α-actin,and fibulin-2. Using a recombinant IL-1α at 5 ng/ml,itwas shown that IL-1α would upregulate,while IL-1 Ra, anIL-1 receptor antagonist, would down一regulate the ex-pression of IL-1a mRNA in MG2 cells, indicating the pres-ence of an autostimulatory loop of IL-1α in these cells.Besides, a paracrine source of IL-1 may be producedfrom Kupffer cells, as we showed primarily culturedKupffer cells responded much more remarkably thanMG2 cells to lipopolysaccharide stimuli to produce bothIL-1α and IL-1β. Recombinant IL-1α upregulated the ex-pression of both MMP-9 and-13, and the induction ofMMP-13 but not MMP-9 could be inhibited by SB203580,an inhibitor of p38. Similarly, in primarily cultured hu-man liver MFs, upregulation of MMP-1 by IL-1α was alsoshown to be inhibited by SB203580. All of these datasuggested that, during liver inflammation,IL-1 producedby an autocrine model from MFs or by a paracrine modelfrom Kupffer cells might play a crucial role in the remod-eling of liver fibrosis through an either p38-dependent orp38-independent pathway to regulate the expression ofvarious MMPs by liver MFs.
- 中文關鍵字: --
- 英文關鍵字: Hepatic stellate cells. Myofibroblast. Kupffer cells. Interleukin-1. Matrix metalloproteinase. p38