Abstract
Background Pyroptosis, a novel form of inflammatory programmed cell death, was recently found to be a cause of mucosal barrier defect. In our pervious study, CD147 expression was documented to increase in intestinal tissue of inflammatory bowel disease (IBD). Objective The aim of this study was to determine the function of serum CD147 in pyroptosis. Methods The study group consisted of 96 cases. The centration of CD147, IL-1β, and IL-18 levels in serum was assessed by ELISA. Real-time PCR and WB were performed to analyze the effect of CD147 on pyroptosis. Results In this study, our results showed that CD147 induced cell pyroptosis in intestinal epithelial cells (IECs) by enhancement of IL-1β and IL-18 expression and secretion in IECs, which is attributed to activation of inflammasomes, including caspase-1 and GSDMD as well as GSDME, leading to aggregate inflammatory reaction. Mechanically, CD147 promoted phosphorylation of NF-κB p65 in IECs, while inhibition of NF-κB activity by the NF-κB inhibitor BAY11-7082 reversed the effect of CD147 on IL-1β and IL-18 secretion. Most importantly, serum CD147 level is slightly clinically correlated with IL-1β, but not IL-18 level. Conclusion These findings revealed a critical role of CD147 in the patients with IBD, suggesting that blockade of CD147 may be a novel therapeutic strategy for the patients with IBD.
Highlights
It is well known that inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD) [1], is a chronic abnormal inflammatory disease of the gastrointestinal tract and remains the principal cause of cancer-related death in the world [2,3,4]
BioMed Research International and tissue damage in IBD, and IL-1β induced defects in intestinal epithelial tight junctions resulting in increased intestinal permeability [15], while IL-18 has been shown to contribute to the breakdown of the mucosal barrier, triggering inflammation and amplifying damage elicited to the intestinal epithelium during disease [16]
We have demonstrated that CD147 is increased in the intestinal mucosa of patients with IBD, which is correlated with DAI
Summary
It is well known that inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD) [1], is a chronic abnormal inflammatory disease of the gastrointestinal tract and remains the principal cause of cancer-related death in the world [2,3,4]. The clinical studies have shown that correlation between increased epithelial secretion of IL-18 and increased severity of IBD suggests that IL-18 may play a key pathogenic role in inflammatory disorders, such as CD [17]. There are two distinct signaling pathway-derived pyroptosis types, either canonical pyroptosis or noncanonical pyroptosis [18,19,20] These findings showed that pyroptosis plays an importantly role in IBD. Our results showed that CD147 induced cell pyroptosis in intestinal epithelial cells (IECs) by enhancement of IL-1β and IL-18 expression and secretion in IECs, which is attributed to activation of inflammasomes, including caspase-1 and GSDMD as well as GSDME, leading to aggregate inflammatory reaction. These findings revealed a critical role of CD147 in the patients with IBD, suggesting that blockade of CD147 may be a novel therapeutic strategy for the patients with IBD
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