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 ono, Masaki Kato, Kazuhiko Nakamura, Koichi Suzuki, Ryoichi Takayanagi, Robert T. Jensen

研究成果: ジャーナルへの寄稿記事

8 引用 (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.

元の言語英語
ページ(範囲)708-719
ページ数12
ジャーナルPancreas
43
発行部数5
DOI
出版物ステータス出版済み - 1 1 2014

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Pancreatic Stellate Cells
Chronic Pancreatitis
Pancreas
Chemokine CX3CL1
Pancreatitis
Cell Proliferation
Acinar Cells
Bromodeoxyuridine
Chemokines
Real-Time Polymerase Chain Reaction
Cytoplasm

All Science Journal Classification (ASJC) codes

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

これを引用

Pancreatic stellate cells and CX3CR1 : Occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist. / Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; ono, takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T.

:: Pancreas, 巻 43, 番号 5, 01.01.2014, p. 708-719.

研究成果: ジャーナルへの寄稿記事

Uchida, M, Ito, T, Nakamura, T, Hijioka, M, Igarashi, H, ono, T, Kato, M, Nakamura, K, Suzuki, K, Takayanagi, R & Jensen, RT 2014, 'Pancreatic stellate cells and CX3CR1: Occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist', Pancreas, 巻. 43, 番号 5, pp. 708-719. https://doi.org/10.1097/MPA.0000000000000109
Uchida, Masahiko ; Ito, Tetsuhide ; Nakamura, Taichi ; Hijioka, Masayuki ; Igarashi, Hisato ; ono, takamasa ; Kato, Masaki ; Nakamura, Kazuhiko ; Suzuki, Koichi ; Takayanagi, Ryoichi ; Jensen, Robert T. / Pancreatic stellate cells and CX3CR1 : Occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist. :: Pancreas. 2014 ; 巻 43, 番号 5. pp. 708-719.
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abstract = "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.",
author = "Masahiko Uchida and Tetsuhide Ito and Taichi Nakamura and Masayuki Hijioka and Hisato Igarashi and takamasa ono and Masaki Kato and Kazuhiko Nakamura and Koichi Suzuki and Ryoichi Takayanagi and Jensen, {Robert T.}",
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T1 - Pancreatic stellate cells and CX3CR1

T2 - Occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

AU - Uchida, Masahiko

AU - Ito, Tetsuhide

AU - Nakamura, Taichi

AU - Hijioka, Masayuki

AU - Igarashi, Hisato

AU - ono, takamasa

AU - Kato, Masaki

AU - Nakamura, Kazuhiko

AU - Suzuki, Koichi

AU - Takayanagi, Ryoichi

AU - Jensen, Robert T.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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