Elucidating the Expression and Role of Epithelial‐Derived Gasdermin‐B (GSDMB) in the Context of Chronic Intestinal Inflammation

Abstract

Inflammatory bowel disease (IBD) represents a group of disorders that results in chronic, uncontrollable inflammation of the gastrointestinal (GI) tract. Despite recent advances, the precise etiology of the two major forms of IBD, Crohn's disease and ulcerative colitis, remains elusive. Gasdermin‐B (GSDMB), a novel molecule belonging to the Gasdermin family of proteins, has gained recent interest for its potential role in the pathogenesis and progression of chronic inflammatory disorders, particularly those that affect mucosal surfaces. Importantly, single nucleotide polymorphisms (SNPs) within the gene encoding for GSDMB have been reportedly associated with increasing the incidence of both asthma and IBD. Here, we aim to examine the aberrant expression and function of epithelial‐derived GSDMB towards the development and progression of chronic intestinal inflammation, such that observed in IBD. Using primary biopsy specimens derived from IBD patients, we confirmed the localization of GSDMB to primarily intestinal epithelial cells (IECs), both in protein and mRNA forms, via western‐blot techniques and immunohistochemistry staining. Moreover, preliminary evidence suggests an inflammasome dependent regulation of GSDMB (similar to that of the closely related GSDMD protein), via stimulation of IEC lines using lipopolysaccharides (LPS) and nigericin treatments to increase GSDMB mRNA expression. Due to the pore‐forming ability of the Gasdermin family of proteins, we suggest increased GSDMB expression may act as a membrane‐bound protein to facilitate the disruption of mucosal barrier function (i.e. restitution and repair), and act as conduit for release of inflammatory cytokines during the progression of IBD. Taken together, this data confirms an increased expression of epithelial‐derived GSDMB in the setting of chronic intestinal inflammation, providing indication for the role of GSDMB towards the development of inflammation within the gut mucosa during IBD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.