MCP-1 INHIBITS DNA SYNTHESIS IN RAT PANCREATIC STELLATE CELLS

IR HANDLE Web Site

Search this article

Abstract

Activated pancreatic stellate cells (PSCs) synthesize various kinds of cytokines and chemokines including monocyte chemoattractant protein-1 (MCP-1) and play major roles in promoting inflammation and fibrogenesis in the pancreas. MCP-1 is a potent chemotactic factor for leukocytes and it has recently been shown that the target is not restricted. The aim of this study was to investigate whether MCP-1 exerts a biological effect on PSCs. Cultured rat PSCs secreted MCP1 independent of the concentration of transforming growth factor-β1 (TGF-β 1) in the culture media. Although PSCs lack the typical receptor system (C-C chemokine receptor 2 (CCR2)), MCP-1 inhibited DNA synthesis in PSCs without activation, suggesting the presence of CCR2-independent MCP-1 signaling pathway. Further, MCP-1 inhibited the proliferation of PSCs in which TGF-β 1/Smad pathway was blocked by the dominant-negative Smad2/3 over-expression. MCP-1 did not affect the phosphorylation state of mitogen-activated protein kinase (MAPK), Akt, nor epidermal growth factor receptor (EGFR). Taken together, MCP-1 inhibited DNA synthesis of cultured rat PSCs in an autocrine or paracrine manner without activation and this effect was exerted through CCR2-independent and TGF-β1/Smad-independent pathway. These data provide new insights to better understand MCP-1 participation in pancreatic inflammation and also to develop a new strategy for its treatment.

Journal

  • 秋田医学

    秋田医学 36 (3-4), 185-194, 2010-03-01

    秋田医学会

Keywords

Details 詳細情報について

Report a problem

Back to top