Existence of autocrine loop between interleukin-6 and tranforming growth factor-β1 in activated rat pancreatic stellate cells

✍ Scribed by Hiroyoshi Aoki; Hirohide Ohnishi; Kouji Hama; Satoshi Shinozaki; Hiroto Kita; Hironori Yamamoto; Hiroyuki Osawa; Kiichi Sato; Kiichi Tamada; Kentaro Sugano

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 173 KB
• Volume: 99
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20906

✦ Synopsis

Abstract

Interleukin (IL)‐6 is a proinflammatory cytokine assumed to participate in pancreatic fibrosis by activating pancreatic stellate cells (PSCs). Autocrine TGF‐β~1~ is to central in PSC functional regulation. In this study, we examined IL‐6 secretion from culture‐activated rat PSCs and its regulatory mechanism. Activated PSCs express and secrete IL‐6. When anti‐TGF‐β~1~ neutralizing antibody was added in the culture medium, IL‐6 secretion from activated PSCs was inhibited, whereas exogenous TGF‐β~1~ added in the culture medium enhanced IL‐6 expression and secretion by PSCs in a dose dependent manner. Infection of PSCs with an adenovirus expressing dominant‐negative Smad2/3 attenuated basal and TGF‐β~1~‐stimulated IL‐6 expression and secretion of PSCs. We also demonstrated the reciprocal effect of PSCs‐secreted IL‐6 on autocrine TGF‐β~1~. Anti‐IL‐6 neutralizing antibody inhibited TGF‐β~1~ secretion from PSCs. Preincubation of cells with 10 nM PD98059, an extracellular signal‐regulated kinase (ERK)‐dependent pathway inhibitor, attenuated IL‐6‐enhanced TGF‐β~1~ expression and secretion of PSCs. In addition, IL‐6 activated ERK in PSCs. These data indicate the existence of autocrine loop between IL‐6 and TGF‐β~1~ through ERK‐ and Smad2/3‐dependent pathways in activated PSCs. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.