細懸浮微粒長期暴露對腸道慢性發炎與新冠病毒重症的潛在影響-ACE2與發炎小體的角色

In the past decade, air pollution is a vital public health issue. In Taiwan, we cannot ignore the health impacts of air pollution according to the air quality index monitored by Environmental Protection Administration. Accumulated evidences showed that air pollution not only affect cardiovascular and respiratory system but also associated with intestinal inflammatory diseases. Recent study demonstrated that increasing angiotensin-converting enzyme 2 (ACE2) levels may involve in the pathogenesis of chronic intestinal inflammation and colorectal cancers. Meanwhile, ACE2 act as receptor of COVID-19 virus for entrance into host cells. However, the detail mechanisms of ACE2 in chronic intestinal inflammation and severe COVID-19 under long term exposure of air pollution are still unclear. Our preliminary results showed that long term PM2.5 exposure trigger persist oxidative stress and inflammations in colonic epithelial cells. The protein levels of NF-kB P65, Cyclooxygenase-2 (COX-2) and ACE2 were raised after PM2.5 treatments for long term exposure. Moreover, PM2.5 impaired autophagy flux and induced inflammasome activation. Hence, our primary goal is to investigate the potential effects of long-term exposure of air pollution induced chronic intestinal inflammations and severe COVID-19. We propose two major aims, respectively, AIM1: to establish long-term exposure to air pollution in vitro model. We will clarify the molecular mechanisms of chronic inflammations triggered by long term air pollution exposure, which mainly focus on the roles of autophagy and ACE2 involved in inflammasome in colorectal epithelial cells. AIM2: To establish colitis-associated cancer of mice with azoxymethane (AOM)/dextran sulfate sodium (DSS) and PM2.5 co-exposures. We will determine molecular mechanism of PM2.5 strengthen chronic inflammations in this in vivo model. Moreover, we will figure out whether ACE2 and autophagy involve in chronic inflammation upon long term PM2.5 exposures. Therefore, our study will provide scientific evidence to determine the potential effects of long-term air pollution exposure in chronic intestinal inflammation and severe COVID-19.