A New Participant in the Pathogenesis of Alcoholic Gastritis: Pyroptosis

Abstract

Background/Aims: Alcohol abuse exerts deleterious effects on the internal organs of the body, and alcohol-related gastritis is a common disease for which prompt treatment is essential to prevent the condition from growing worse. However, the therapeutic methods have some adverse effects. Determining the pathogenic mechanisms of alcoholic gastritis is therefore essential. Methods: The MTT assay was developed in order to determine the optimal concentration of alcohol needed to treat gastric mucosal cells. The effects of alcohol on the gastric mucosal cells were determined by qRT-PCR and western blot. The release of IL-1β and IL-18 were determined by ELISA assay. The immunofluorescence assay was used to detect caspase-1 activation levels, while immunohistochemical assay and HE staining were performed to identify the effectiveness of the caspase-1 inhibitor on alcoholic gastritis. The TUNEL assay was used to determine DNA fragmentation. Results: Here, we clarified that ethanol treatment could cause cell DNA damage, activate caspase-1, and promote the generation and release of IL-1β and IL-18. In other words, ethanol could induce pyroptosis. Interestingly, a caspase-1 inhibitor could significantly suppress pyroptosis, decrease the release of inflammatory cytokines induced by ethanol, and cause no side effects in vivo and in vitro. Conclusion: Collectively, our results showed that pyroptosis is involved in the pathogenesis of alcohol-induced gastritis and that caspase-1 inhibitor Ac-yvad-cmk could effectively decrease the damage caused by alcohol, making it a potentially promising agent for the treatment of alcoholic gastritis.