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2007 Fiscal Year Final Research Report Summary

Activation of pancreatic stellate cells mediated by Toll-like receptor

Research Project

Project/Area Number 18590712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTohoku University

Principal Investigator

MASAMUNE Atsushi  Tohoku University, TOHOKU UNIVERSITY HOSPITAL, Assistant Professor (90312579)

Co-Investigator(Kenkyū-buntansha) SATOH Kennichi  TOHOKU UNIVERSITY HOSPITAL, 病院, Assistant Professor (10282055)
Project Period (FY) 2006 – 2007
KeywordsPancreatic stellate cells / Pancreatic fibrosis / Chronic pancreatitis
Research Abstract

Toll-like receptors (TLRs) are proteins involved in recognition of foreign pathogen-associated molecular patterns (PAMPs) and activation of innate immunity. This study aimed to clarify whether pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, expressed TLRs and responded to PAMPs. PSC were isolated from rat pancreas tissue, and expression of TLRs was examined. PSCs were treated with lipoteichoic acid (a ligand for TLR2), polyinosinic-polycytidylic acid (a ligand for TLR3), lipopolysaccharide (a ligand for TLR4), or flagellin (a ligand for TLR5). The effects of the TLR ligands were examined on the activation of nuclear factor-κB and mitogen-activated protein kinases, chemokine production, and expression of inducible nitric oxide synthase. The ability to perform endocytosis and phagocytosis was also examined. PSCs expressed TLR2, 3, 4, and 5, as well as associated molecules CD14 and MD2. All of the TLR ligands activated nuclear factor-κB and three classes of mitogen-activated protein kinases (extracellular-signal regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase). TLR ligands induced the expression of monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant-1, and inducible nitric oxide synthase. PSCs could perform fluid-phase and receptor-mediated endocytosis, as well as phagocytosis of E. coli. In conclusion, PSCs expressed a variety of TLRs, and responded to TLR ligands, leading to the activation of signaling pathways and proinflammatory responses. PSCs could process exogenous antigens by endocytosis and phagocytosis. PSCs might play a role in the immune functions of the pancreas through the recognition of PAMPs.

  • Research Products

    (6 results)

All 2008 2007

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] NADPH oxidase plays a crucial role in the activation of pancreatic stellate Cells.2008

    • Author(s)
      Masamune A, et. al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 294

      Pages: G99-G108

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells express Toll-like receptors.2008

    • Author(s)
      Masamune A, et. al.
    • Journal Title

      J Gastroenterol 43(In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Pancreatic stellate cells express Toll-like receptors2008

    • Author(s)
      Masamune A. Kikuta K, Watanabe T, Satoh K, Satoh A, Shimosegawa T.
    • Journal Title

      J Gastroenterol 43

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells2008

    • Author(s)
      Masamune A. Watanabe T, Kikuta K, Satoh K, Shimosegawa T.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 294

      Pages: 99-108

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Hypoxia induces collagen production in pancreatic stellate cells.2007

    • Author(s)
      Masamune A, et. al.
    • Organizer
      Digestive Diseases Week
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2007-05-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Hypoxia induces Collagen production in pancreatic stellate cells2007

    • Author(s)
      Masamune A, Kikuta K. Watanabe T, Shimosegawa T
    • Organizer
      Digestive Disease Week 2007
    • Place of Presentation
      Washington, DC. USA
    • Year and Date
      2007-05-18
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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