Involvement of the epidermal growth factor receptor in Pb2+-induced activation of cPLA2/COX-2 genes and PGE2 production in vascular smooth muscle cells

Wei Chiao Chang, Chen Chia Chang, Yung Song Wang, Yu Shiuan Wang, Wei Teng Weng, Tohru Yoshioka, Suh Hang Hank Juo

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

摘要

Lead (Pb2+) is one of the most common heavy metal pollutants, which can cause chronic cardiovascular diseases. To clarify the mechanism by which Pb2+ induces inflammatory reactions, we examined the expression of inflammatory genes including encoding cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), and their down stream product prostaglandin E2 (PGE2) in CRL1999 cells that is a vascular smooth muscle cell line from human aorta. The expression of COX-2/cPLA2 genes and PGE2 secretion was increased markedly after cells were exposed to 1μM Pb2+. PD098059, a MEK inhibitor, suppressed Pb2+-mediated inflammatory reactions; this indicates the involvement of the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Furthermore, Pb2+-induced activation of the COX-2/cPLA2 genes was inhibited by both epidermal growth factor receptor (EGFR) inhibitors (AG1478 and PD153035) and EGFR siRNA. Short-term stimulation with Pb2+ induced EGFR phosphorylation at the Tyr residue (position, 1173). Importantly, overexpression of EGFR resulted in a significant potentiation effect on Pb2+-induced gene expression. Taken together, our results indicate that 1μM Pb2+ can induce PGE2 secretion by upregulating the transcription of COX-2/cPLA2 genes. EGFR is the key target in the plasma membrane responsible for transmitting Pb2+ signals in order to trigger downstream inflammatory cascades.
原文英語
頁(從 - 到)45-53
頁數9
期刊Toxicology
279
發行號1-3
DOIs
出版狀態已發佈 - 1月 11 2011
對外發佈

ASJC Scopus subject areas

  • 毒理學

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