Studies On The Molecular Mechanism Of The Benzo [a] pyrene –Induced Socs3 Expression Via AhR / Stat3 Pathway In ARPE-19 Cells

• Main Authors: Yi Lee, 李儀
• Other Authors: 康照洲
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/6ysqmm

碩士 === 國立臺灣大學 === 毒理學研究所 === 106 === Recently, studies demonstrated that PAHs might increase a number of eye lesions. Statistics of epidemics suggested that smoking was a risk factor for oculardiseases. Benzo[a]pyrene (B[a]P), one of the polycyclic aromatic hydrocarbons (PAHs), a carcinogenic chemical substance that is widely present in the environment. It is produced by incomplete combustion of carbon. B[a]P is an aryl hydrocarbon receptor (AhR) ligand that binds to the AhR protein and further regulates downstream gene transcription. In addition, studies had also shown that B[a]P might affect the cellular inflammatory response through activation of the AhR pathway, but the relevant mechanisms remained unclear. Suppressor of cytokine signaling-3 (Socs3), an inflammatory regulator, act as an inhibitor of inflammation by negative feedback. Inflammation is one of the major causes of retinopathy. Therefore, this study aims to observe the effect of the AhR –regulated Socs3 pathway with B[a]P exposure. Here, we used ARPE-19 human retinal pigment epithelial cell line that B[a]P induced Socs3 expression through the activation of AhR. Knock out of AhR attenuated the B[a]P-dependent induction of Socs3 expression, accompanied with the increase of the phosphorylated Stat3. Subsequent experiments using immunofluorescence and Stat3 phosphorylation inhibitors demonstrated that in the absence of AhR, activation of Stat3 replaced AhR and increased the expression of Socs3. In addition, after exposure to 3 μM B[a]P for 24 hours, inflammatory cytokines IL-6 and TGF-beta1 were measured and no change in the protein expression was found. More studies should be done to further confirm the effect of B[a]P to ARPE-19 cells.