Identification of Molecular Mechanisms for Environmental Toxicants in Inflammatory Genes

• Main Authors: Jhen-Hong Wong, 翁禎宏
• Other Authors: Jaw-Yuan Wang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/00944929816073801881

碩士 === 高雄醫學大學 === 醫學遺傳學研究所 === 101 === The environment is filled with toxic factors, such as heavy metals, microbes, food additives, and these substances can cause immune diseases and inflammatory reactions in human. Lead (Pb2+), a common heavy metal, is widely used in many products, such as cosmetics, tableware and car battery. The lead poisoning resulted in nausea, vomiting, increased blood pressure. Continuous exposure to lead can cause multiple neuropathy and brain lesions. To further clarify the role of lead in cellular molecular mechanisms, we treated human epidermoid carcinoma cell line (A431) with lead ions to investigate whether leads can activate IL-8 gene expression and its signaling pathway. We found that Pb2+ ions incite inflammation by inducing IL-8 gene expression via the EGFR-ERK1/2-AP1 cellular transduction pathways. In another study regarding effects of microbial toxins on human bodies, we used the human stomach adenocarcinoma cell line (AGS) to investigate whether lipopolysaccharide (LPS), a bacterial endotoxin, can activate COX-2 gene expression and relative signaling pathways. Our results indicated that LPS incites inflammation by inducing COX-2 gene expression via the ERK1/2-NFκB cellular signaling pathways. Besides the lead and LPS, exposing human body to PAEs, which are usually used to increase the toughness and ductility of plastic products, may also cause inflammation and even asthma, allergy symptoms and reproductive dysfunction. Herein, AGS cells were treated by PAEs derivatives, di(2-ethylhexyl)phthalate, to investigate whether the PAEs can activate COX-2 gene expression. In this study we found that di(2-ethylhexyl)phthalate induces inflammation by activation of COX-2 gene expression via ERK1/2-NFκB pathways.