To study the role of COX-2 in PM2.5-induced chronic intestinal inflammation and cell proliferation

In recent years, the levels of particulate matter (PM) detected in Taiwan has indicated that the health effects of air pollution cannot be ignored. Many studies have shown that exposure to air pollution is a significant threat to the health around the world. Since PM2.5 can enter into the human gut from the lungs via the mucociliary transport system, PM may be associated with intestinal inflammatory diseases. Recent studies have demonstrated that exposure to PM2.5 may cause oxidative stress and inflammation in intestinal cells, result in alterations of permeability of intestinal epithelial cells and the microbiota compositions. The oxidative stress-induced inflammation also changes the homeostasis of intestinal immunity system. The gut microbes can invade into deeper tissues leading to infiltrations of immune cells and massive inflammations. Our preliminary results showed that long term PM2.5 exposures increased cyclooxygenase-2 (COX-2) expressions and autophagic pathway in colorectal carcinoma WiDr cells. An elevated COX-2 expression was found in colorectal cancer tissue and also act as a prospective prognostic indicator. Therefore, this proposal will establish long term exposures of PM in colorectal carcinoma WiDr cells to investigate the roles of COX-2 in chronic gut inflammation and cell proliferations. Meanwhile, we will also determine the interplay between autophagy and COX in PM-induced chronic gut inflammations. This study will clarify whether air pollution will be a risk factor for colorectal cancer and determine the detail molecular mechanism of adverse effects of PM in colorectal cancer.