Activation and induction of cytosolic phospholipase A2 by IL-1β in human tracheal smooth muscle cells: Role of MAPKs/p300 and NF-κB

Chiang Wen Lee, I. Ta Lee, Chih Chung Lin, Hui Chun Lee, Wei Ning Lin, Chuen Mao Yang

研究成果: 雜誌貢獻文章

15 引文 斯高帕斯(Scopus)

摘要

Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by IL-1β. However, the mechanisms underlying IL-1β-induced cPLA2 expression and PGE2 synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. IL-1β-induced cPLA2 protein and mRNA expression, PGE2 production, or phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, which was attenuated by pretreatment with the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNAs of MEK1, p42, p38, and JNK2. IL-1β-induced cPLA2 expression was also inhibited by pretreatment with a NF-κB inhibitor, helenalin or transfection with siRNA of NIK, IKKα, or IKKβ. IL-β-induced NF-κB translocation was blocked by pretreatment with helenalin, but not U0126, SB202190, and SP600125. In addition, transfection with p300 siRNA blocked cPLA2 expression induced by IL-1β. Moreover, p300 was associated with the cPLA2 promoter, which was dynamically linked to histone H4 acetylation stimulated by IL-1β. These results suggest that in HTSMCs, activation of MAPKs, NF-κB, and p300 are essential for IL-1β-induced cPLA2 expression and PGE2 secretion.
原文英語
頁(從 - 到)1045-1056
頁數12
期刊Journal of Cellular Biochemistry
109
發行號5
DOIs
出版狀態已發佈 - 四月 1 2010
對外發佈Yes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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