Bile Acids and Bile Acid Metabolites in the Activation and Inhibition of Pyroptotic Cell Death, Influencing Inflammation

Abstract

Pyroptosis is a lytic and pro-inflammatory regulated cell death pathway mediated by pores formed by the oligomerization of gasdermin proteins on cellular membranes. Different pro-inflammatory molecules such as interleukin-18 are released from these pores, promoting inflammation. Pyroptotic cell death has been implicated in many pathological conditions, including cancer and liver diseases. Bile acids are amphipathic cholesterol-derived molecules, regulating many biological processes due to their unique structures and functions. Increasing data has recently shown that bile acids have additional novel functions besides their classical role as a lipid solubilizer in dietary lipid digestion. In the present review, primary and secondary bile acids that have been shown to be involved either in the activation or in the inhibition of pyroptotic cell death in diverse cell types and contexts, thereby modulating inflammation, were covered. Besides, their mechanisms of action in pro-inflammatory cell death and subsequent inflammation were detailed. These studies together point out that different bile acids might influence pyroptotic events in varied ways (either positively or negatively) depending on different parameters such as the type of bile acid, via distinct downstream players and molecular processes. A more complete understanding of bile acid-induced changes in pyroptotic events in different disease conditions is needed.