Inflammatory caspase-related pyroptosis: Mechanism, regulation and therapeutic potential for inflammatory bowel disease

Abstract

As an essential part of programmed cell death, pyroptosis is an inflammatory response that is elicited upon infection by intracellular pathogens. Metabolic diseases, atherosclerosis and vital organ damage occur if pyroptosis is over-activated. Macrophages are the main cells that induce pyroptosis with the help of intracellular pattern-recognition receptors stimulated by danger signals and pathogenic microorganisms in the cytosol of host cells. Activated inflammatory caspases induce pyroptosis and produce pro-inflammatory cytokines, such as interleukin-1b and interleukin-18. Inflammatory programmed cell death is classified as canonical or non-canonical based on inflammatory caspases, which includes caspase-1 (in human and mouse) and caspase-11 (in mouse) or caspase-4 and -5 (in humans). Activated inflammatory caspases cleave the pore-forming effector protein, gasdermin-D, inducing osmotic pressure deregulation of internal fluids and subsequently rupturing the cell membranes. Inflammatory caspases could be attractive therapeutic targets for inflammatory bowel disease (IBD) in which pyroptosis may play an important role. This article reviews the current understanding of the mechanism of pyroptosis, focusing on the regulation of inflammatory caspases and therapeutic strategies for IBD.