Pancreatic stellate cells and CX3CR1: Occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

Masahiko Uchida, Tetsuhide Ito, Taichi Nakamura, Masayuki Hijioka, Hisato Igarashi, Takamasa Oono, Masaki Kato, Kazuhiko Nakamura, Koichi Suzuki, Ryoichi Takayanagi, Robert T. Jensen

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)

抄録

OBJECTIVES: Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the effects of CX3CL1 on activated PSCs. METHODS: CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated PSCs were examined with real-time polymerase chain reaction, BrdU (5-bromo-2-deoxyuridine) assays, and Western blotting. RESULTS: In normal pancreas, acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not induce inflammatory genes expression in activated PSCs, but induced proliferation. CONCLUSIONS: CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1 induces proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSC proliferation in pancreatitis where CX3CL1 levels are elevated.

本文言語英語
ページ(範囲)708-719
ページ数12
ジャーナルPancreas
43
5
DOI
出版ステータス出版済み - 7月 2014

!!!All Science Journal Classification (ASJC) codes

  • 内科学
  • 内分泌学、糖尿病および代謝内科学
  • 肝臓学
  • 内分泌学

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