IS-741 attenuates local migration of monocytes and subsequent pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats

Toyoma Kaku, Takamasa Oono, Haifeng Zhao, Junya Gibo, Ken Kawabe, Tetsuhide Ito, Ryoichi Takayanagi

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8 Citations (Scopus)

Abstract

OBJECTIVES: Chronic pancreatitis consists of excessive leukocyte infiltration and fibrosis. IS-741 has been reported to be an antiinflammatory drug through an inhibitory action on cell adhesion. In this study, we investigated whether IS-741 could inhibit the progression of pancreatic fibrosis through monocyte infiltration. Moreover, we investigated the effect of IS-741 on rat pancreatic stellate cells (PSCs). METHODS: Chronic pancreatitis was induced by dibutyltin dichloride in rats. From days 7 to 28 after dibutyltin dichloride application, IS-741 or distilled water was administered. At days 14 and 28, histological [hematoxylin-eosin stain and immunostain for ED1 and α smooth muscle actin (α-SMA)] and biochemical evaluations (intrapancreatic amylase, protein, cytokines, chemokines, and α-SMA) were performed. In vitro, rat PSCs were incubated with cytokine, chemokine, and growth factor simultaneously with IS-741, and their proliferation and activation were examined. RESULTS: Histologically, IS-741 inhibited pancreatic fibrosis and decreased the number of ED1- and α-SMA-positive cells. The intrapancreatic expression of cytokines, chemokine, and α-SMA were also decreased. In vitro, IS-741 has no direct effect on the proliferation, α-SMA expression, and collagen synthesis of PSCs. CONCLUSIONS: These results suggest that IS-741 suppressed macrophage infiltration and subsequent pancreatic fibrosis and that the infiltration of monocytes into pancreas is essential for pancreatic fibrosis.

Original languageEnglish
Pages (from-to)299-309
Number of pages11
JournalPancreas
Volume34
Issue number3
DOIs
Publication statusPublished - Apr 2007

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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