The molecular mechanism of Pb2+-induced inflammatory genes

• Main Authors: Yao-Ting Tsai, 蔡耀庭
• Other Authors: Wei-chiao chang
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/04606004924392357061

碩士 === 高雄醫學大學 === 醫學遺傳學研究所 === 100 === In our life, the metal lead is widely used in many things, such as detergents, cosmetics, tableware, toys. Divalent lead cations may contribute to inflammatory diseases in people and animals. To further clarify the mechanism by which Pb2+ induces such mediators of inflammation, we tested human epidermoid carcinoma cell line A431. We found Pb2+ ions incite inflammation by inducing COX-2 gene expression via the EGFR/ NF-κB signal transduction pathway. Furthermore, Pb2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via EGFR and transcription factors Rb and E2F1. In lead poisoning patients, gastralgia or gastritis made them uncomfortable. To further clarify the molecular mechanism by which Pb2+ induces gastrin gene expression, we tested human Stomach Adenocarcinoma cell line AGS. Our finding highlights the ERK1/2 and AP1 pathways, and its potential role in Pb2+-induced gastrin gene expression. According to our results, the EGFR played an important role in Pb2+-induced inflammatory genes expression. The association between EGFR SNPs and lead poisoning patients is unclear. Our results indicated that EGFR genetic polymorphism had no association with the lead poisoning patients.