Cigarette smoke extract induces COX-2 expression via a PKCα/c-Src/ EGFR, PDGFR/PI3K/Akt/NF-κB pathway and p300 in tracheal smooth muscle cells

Chuen Mao Yang, I. Ta Lee, Chih Chung Lin, Ya Lin Yang, Shue Fen Luo, Yu Ru Kou, Li Der Hsiao

研究成果: 雜誌貢獻文章同行評審

61 引文 斯高帕斯(Scopus)

摘要

Exposure to cigarette smoke extract (CSE) leads to airway or lung inflammation, which may be mediated through cyclooxygenase-2 (COX-2) expression and its product prostaglandin E2 (PGE2) synthesis. The aim of this study was to investigate the molecular mechanisms underlying CSE-induced COX-2 expression in human tracheal smooth muscle cells (HTSMCs). Here, we describe that COX-2 induction is dependent on PKCα/c-Src/EGFR, PDGFR/PI3K/Akt/NF-κB signaling in HTSMCs. CSE stimulated the phosphorylation of c-Src, EGFR, PDGFR, and Akt, which were inhibited by pretreatment with the inhibitor of PKCα (Gö6976 or Gö6983), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), or PI3K (LY294002). Moreover, CSE induced a significant increase in COX-2 expression, which was reduced by pretreatment with these inhibitors or transfection with siRNA of PKCα, Src, or Akt. Furthermore, CSE-stimulated NF-κB p65 phosphorylation and translocation were also attenuated by pretreatment with Gö6976, PP1, AG1478, AG1296, or LY294002. CSE-induced COX-2 expression was also mediated through the recruitment of p300 associated with NF-κB in HTSMCs, revealed by coimmunoprecipitation and Western blot analysis. In addition, pretreatment with the inhibitors of NF-κB (helenalin) and p300 (garcinol) or transfection with p65 siRNA and p300 siRNA markedly inhibited CSE-regulated COX-2 expression. However, CSE-induced PGE2 generation was reduced by pretreatment with the inhibitor of COX-2 (NS-398). These results demonstrated that in HTSMCs, CSE-induced COX-2-dependent PGE2 generation was mediated through PKCα/c-Src/EGFR, PDGFR/PI3K/Akt leading to the recruitment of p300 with NF-κB complex.
原文英語
頁(從 - 到)L892-L902
期刊American Journal of Physiology - Lung Cellular and Molecular Physiology
297
發行號5
DOIs
出版狀態已發佈 - 十一月 1 2009
對外發佈

ASJC Scopus subject areas

  • 生理學
  • 肺和呼吸系統醫學
  • 細胞生物學
  • 生理學(醫學)

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