The molecular mechanism of Ni2+-induced inflammatory genes

• Main Authors: Chih-Ang Chung, 鍾志昂
• Other Authors: Wei-Chiao Chung
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/43625671607295507858

碩士 === 高雄醫學大學 === 生物化學研究所 === 101 === The metal nickel is everywhere in our daily lives, including coins, costume jewelry, and even nuts and chocolates. Accumulation of nickel ions in the body caused by nickel poisoning in humans or other animals will further cause inflammation, respiratory diseases or allergic contact dermatitis. To clarify the mechanism by which Ni2+ induces mediators of inflammation, we utilized human acute monocytic leukemia cell line THP-1 as a model. We found Ni2+ ions induced inflammation by inducing IL-8 gene expression via the L-type Ca2+ channel and TLR4 through AP-1 and NFκB signal transduction pathways. Furthermore, in the past study, anti-inflammatory drugs (NSAIDs) was suggested to reduce the risk of breast cancer through inhibition of COX-2. Ni2+ ions have been hypothesized to play a role in breast cancer development by binding to estrogen receptors and mimic the actions of estrogen. Exposure to estrogen is a well-established risk factor for breast cancer. To further clarify the molecular mechanism by which Ni2+ induces COX-2 gene expression, we tested human mammary gland adenocarcinoma epithelial cell line MCF-7. Our finding highlights the involvement of NFκB pathways in Ni2+-induced COX-2 gene expression and cell migration. According to our results, the L-type Ca2+ channel and TLR4 played an important role in Ni2+-induced inflammatory genes expression.