Sting pathway - A futuristic therapeutic target for acute pancreatitis?

Abstract

Acute Pancreatitis (AP) refers to the inflammatory state of the pancreatic mass caused by an abnormal release of digestive enzymes characterized by pancreatic acinar cell injury. It is mainly caused by gallstones, which primarily block sphincter of Oddi opening into the duodenum, heavyalcohol use, systemic diseases, etc. Stimulator of interferon genes known as STING uniquely senses the apoptotic and necrotic DNA fragments. Through the expression of TMEM173 (transmembrane protein 173) or STING protein in macrophages, downstream signaling pathways are activated in AP and are responsible for promoting inflammation. STING elicits a cascade of downstream signaling events such as activation of TBK1, IRF-3 phosphorylation, and IFN-β production along with other cytokines, which result in the excessive manufacture of the type-I IFNs and different kinds of proinflammatory cytokines that take part in the immune defense system of the host. Research findings suggest that STING regulates an array of innate immunity pathways, and the absence of proper treatment measures for AP provides the opportunity of evaluating STING as a striking therapeutic target for AP associated inflammation. Although the understanding of STING hyperactivation and its association with inflammation is relative of recent interest among researchers, extensive studies are going on to identify inhibitors that can directly target STING and inhibits the downstream signaling in AP. Therefore, this review aims to collectively compile the available pieces of evidence, which could help to better understand the role of STING signaling in AP and its promising role as a therapeutic target.