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

Yii Her Chou, Peng Yeong Woon, Wan Chen Huang, Robert Shiurba, Yao Ting Tsai, Yu Shiuan Wang, Tusty Jiuan Hsieh, Wen Chang Chang, Hung Yi Chuang, Wei Chiao Chang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Divalent lead cations (Pb 2+) 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 Pb 2+ ions by activating mediators of inflammation via the plasma membrane epidermal growth factor receptor (EGFR). These include cyclooxygenase-2 (COX-2) and cytosolic phospholipase A 2 as well as the hormone-like lipid compound prostaglandin E 2. To further clarify the mechanism by which Pb 2+ 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 (1μM) of Pb 2+ 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 Pb 2+-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.

Original languageEnglish
Pages (from-to)147-153
Number of pages7
JournalToxicology Letters
Volume203
Issue number2
DOIs
Publication statusPublished - Jun 10 2011
Externally publishedYes

Keywords

  • Cyclooxygenase-2
  • EGFR
  • Lead

ASJC Scopus subject areas

  • Toxicology

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