Divalent lead cations induce cyclooxygenase-2 gene expression by epidermal growth factor receptor/nuclear factor-kappa B signaling in A431carcinoma cells

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• 作者：Yii-Her Chou^g ; ¹ ; Peng-Yeong Woon^f ; ¹ ; Wan-Chen Huang^d ; ¹ ; Robert Shiurba^h ; Yao-Ting Tsai^a ; Yu-Shiuan Wang^a ; Tusty-Jiuan Hsieh^a ; Wen-Chang Chang^d ; ⁱ ; Hung-Yi Chuang^e ; Wei-Chiao Chang^a ; ^b ; ^c ; ^{wcc@kmu.edu.tw"" rel=""nofollow}
• 关键词：Lead ; EGFR ; Cyclooxygenase-2
• 刊名：Toxicology Letters
• 出版年：2011
• 出版时间：10 June 2011
• 年：2011
• 卷：203
• 期：2
• 页码：147-153
• 全文大小：1045 K

文摘

Divalent lead cations (Pb²⁺) are toxic metal pollutants that may contribute to inflammatory diseases in people and animals. Human vascular smooth muscle cells in culture respond to low concentrations of Pb²⁺ ions by activating mediators of inflammation via the plasma membrane epidermal growth factor receptor (EGFR). These include cyclooxygenase-2 (COX-2) and cytosolic phospholipase A₂ as well as the hormone-like lipid compound prostaglandin E₂. To further clarify the mechanism by which Pb²⁺ induces such mediators of inflammation, we tested human epidermoid carcinoma cell line A431 that expresses high levels of EGFR. Reverse transcription PCR and western blots confirmed A431 cells treated with a low concentration (1 μM) of Pb²⁺ in the form of lead (II) nitrate increased expression of COX-2 mRNA and its encoded protein in a time-dependent manner. Promoter deletion analysis revealed the transcription factor known as nuclear factor-kappa B (NF-κB) was a necessary component of the COX-2 gene response. NF-κB inhibitor BAY 11-7082 suppressed Pb²⁺-induced COX-2 mRNA expression, and EGFR inhibitors AG1478 and PD153035 as well as EGFR small interfering RNA reduced the coincident nuclear translocation of NF-κB. Our findings support the hypothesis that low concentrations of Pb2⁺ ions incite inflammation by inducing COX-2 gene expression via the EGFR/NF-κB signal transduction pathway.