Immune‐compromised state in the rat pancreas after chronic alcohol exposure: the role of peroxisome proliferator‐activated receptor γ

摘要: Alcohol exposure is known to sensitize acinar cells various insults but the pathophysiological mechanisms of alcoholic pancreatitis remain unknown. abuse has been shown mediate an anti-inflammatory response and periods immune suppression seem be associated with organ injury mortality. The purpose this study was determine by which alcohol exerts transcriptional activities in rat pancreas how alters inflammatory response. Using Lieber-DeCarli alcohol/control diet, rats that were fed over 14 weeks demonstrated a decrease pancreatic tissue compared controls. effects confirmed decreased expression pro-inflammatory cytokines including TNFalpha, IL-1beta, IL-18, TGFbeta, MCP-1. In addition, significantly increased activity PPARgamma, transcription factor, while factors AP-2 EGR-1 suppressed. NFkappaB binding showed tendency towards reduction. Electron microscopy studies revealed enlarged injured mitochondria lysosomes, accompanied peri-cellular fibrosis. Furthermore, trypsin cathepsin B, both critical initiating cell pancreatitis. Despite alcohol-mediated mitochondrial injury, mitochondrial-mediated apoptotic pathway attenuated. These data demonstrate exposed maintains state activating PPARgamma. Intracellular lysosomal damage after chronic induces premature activation digestive enzymes establishment fibrosis absence inflammation.