胃粘膜上皮細胞のtrefoil factor family発現に及ぼすindomethacinの影響  [in Japanese] Effect of Indomethacin on TFF Expression in Gastric Epithelial Cells  [in Japanese]

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Abstract

Trefoil factor family(TFF)に属するペプチド(TFF1,TFF2,TFF3)は,消化管粘膜の健常性維持,傷害修復過程に重要な役割を果たしているが,その発現調節については不明の部分が多い。本研究では,胃癌由来細胞株であるMKN45細胞を用いて,胃粘膜傷害の起因因子であるNSAIDsのTFF発現に対する影響をリアルタイム定量的RT-PCR法で解析した。MKN45細胞では,TFF1の発現レベルが最も高く,次いでTFF2であり,TFF3の発現レベルは非常に低かった。IndomethacinはTFF1,TFF3の発現に対しては有意な影響を与えず,TFF2の発現は濃度依存性に上昇させた。IndomethacinによるTFF2発現誘導は他の胃癌由来細胞株(AGS,JR)でも認められ,また,他のNSAIDs (aspirin,NS-398)もMKN45細胞においてTFF2発現を上昇させた。このindomethacinの効果は外来性のPGE2の投与では拮抗されなかった。以上の結果から,NSAIDsはそのCOX抑制作用とは別の機構を介して胃粘膜上皮細胞のTFF2発現を誘導していることが示唆された。NSAIDsの投与によるTFF2発現レベルの上昇は,NSAIDs起因性胃粘膜傷害の発生をある程度防御している可能性が考えられる

Although trefoil factor family (TFF) peptides (TFF1, TFF2, and TFF3) are assumed to play important roles in the protection of gastrointestinal mucosa, regulatory mechanisms of TFF expression are poorly understood at present. In the present study, we examined the effect of indomethacin, a non-selective inhibitor of cyclooxygenase (COX), on the expression of TFF mRNA expression in MKN 45 gastric cells by real-time quantitative RT-PCR method. In MKN 45 cells, relative expression level of TFF1, TFF2, and TFF3 mRNA was 617 : 12 : 1 in the control condition. Indomethacin up-regulated the expression level of TFF 2 in a dose-dependent manner, whereas TFF 1 and TFF 3 expression levels were not significantly affected. Luciferase reporter gene assay confirmed this stimulatory effect of indomethacin on TFF 2 expression. Other COX inhibitors, such as aspirin and NS -398, also up-regulated TFF 2 expression and indomethacin-induced up-regulation of TFF2 expression was also observed in other gatric cell lines, such as AGS and JR. Externally applied PGE2 did not antagonize the effect of indomethacin on TFF2 expression. Since TFF peptides play a critical role in gastric mucosal protection, indomethacin-induced TFF2 may reduce the degree of gastric mucosal damage induced by indomethacin. The present results also suggest that the effect of indomethacin on TFF2 expression is COX-independent.

Journal

  • Dokkyo journal of medical sciences

    Dokkyo journal of medical sciences 30(1), 85-92, 2003-03-25

Codes

  • NII Article ID (NAID)
    110000008686
  • NII NACSIS-CAT ID (NCID)
    AA00629581
  • Text Lang
    JPN
  • Article Type
    journal article
  • ISSN
    0385-5023
  • Data Source
    NII-ELS  IR 
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