| dc.description.abstract | Particulate Matter (PM), as the main air pollutants, is a mixture composed of inorganic and organic components in the air. PM can enter the lungs through the respiratory system and cause lung damage. Also, PM may enter the human intestines from the lungs via the mucociliary transport system, which is also considered to be related to intestinal inflammation. Several studies report that PM exposure is associated with intestinal diseases, including inflammation, increased intestinal permeability and epithelial cell proliferation. However, it is still unclear the relationship and molecular mechanisms between PM and intestinal adverse effects. In this study, we would like to clarify the molecular mechanisms underlying adverse effects associated PM in human colonic epithelial (WiDr) cells. Our result sowed that PM increased the levels of ROS leading to antioxidant enzymes NQO-1 and HO-1 productions, and NF-κB mediated inflammatory response activation. The phosphorylation of p65 and IκBα occurred and then triggered sequentially downstream inflammatory cytokine IL-8 production after PM exposure in WiDr cells. Antioxidants N-acetylcysteine (NAC) pretreatment can reduce the PM-induced IL-8 production. Therefore, our results indicated that ROS involved in PM-induced NF-κB inflammation pathway in colonic epithelial cells. Meanwhile, we found that PM exposure increased intestinal cell proliferation by using BrdU analysis. AKT phosphorylation was also increased after PM exposure. AKT inhibitor, MK2206, pretreatment reduced the PM-increased cell proliferation. Finally, we found that under PM treatment, the expression of autophagy-related proteins LC3-II, Beclin1, and P62 increased. Antioxidants and Autophagy inhibitor 3-Methyladenine (3MA) can reduce IL-8 production and cell proliferation after PM treatment. In summary, PM exposure may cause adverse effects to the intestinal epithelial cells through ROS mediated inflammation, activation of antioxidant mechanisms, cell proliferation, and the production of autophagy. Taken together, our result will help to clarify the underlying molecular mechanisms of adverse effects induced by PM, which may provide scientific evidences to reduce the impacts of PM on public health in the future. | en_US |