Abstract
Background: the 18-kDa translocator protein (TSPO) is a mitochondrial outer membrane protein, and its expression tends to increase in response to inflammatory stimulation, rapidly. However, the role of TSPO in inflammation and pyroptosis is not yet clear. Here, we identified TSPO as a novel key regulator of pyroptosis. (2) Methods: TSPO knockout and DSS induced mouse inflammatory bowel disease (IBD) models were employed to assess the roles of TSPO in the pathogenesis of IBD. Primary peritoneal macrophages from TSPO knockout mice were applied to evaluate the mechanism of TSPO in cell pyroptosis. Conclusions: in response to inflammatory injury, TSPO expression is rapidly upregulated and provides a protective function against GSDMD-mediated pyroptosis, which helps us better understand the biological role of TSPO and a novel regulatory mechanism of the pyroptosis process.
Highlights
The increased disease activity index (DAI) scores were more pronounced in translocator protein (TSPO)-KO mice than in TSPO-wild type (WT) mice (Figure 1B), indicating that weight loss, blood stool, and soft stools were more severe in KO mice than in WT mice
Flow cytometry analysis showed no difference between the proportion of CD11b+ /CD86+ M1 macrophages among lamina propria (LP)
We found that the levels of caspase-1 and GSDMD expression in unstimulated macrophages from WT and TSPO-KO mice were at the same level
Summary
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the intestine that is characterized by continuous inflammation of the mucosal and submucosal layers of the colon and includes Crohn’s disease (CD) and ulcerative colitis (UC). Chronic intestinal inflammation usually involves the rectum first and gradually spreads to the entire colon, while it is accompanied by the activation of inflammasomes [1–4] and the release of cytokines, such as IL-1β, due to pyroptosis [5,6]. When cells are stimulated by inflammatory signals, such as LPS, the downstream inflammasome complex NLRP3 is activated through the classic or nonclassic inflammatory activation pathway and started caspase-1 shears GSDMD to form the N-terminal GSDMD fragment (p30). GSDMD (p30) has pore-forming toxicity and is the final effector protein of GSDMD-mediated pyroptosis [8,9]. Free GSDMD (p30) targets and inserts into the plasma membrane, forming pore-like structures with inner diameters of
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call