Targeting NLRP3 Inflammasome in Inflammatory Bowel Disease: Putting out the Fire of Inflammation
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REVIEW
Targeting NLRP3 Inflammasome in Inflammatory Bowel Disease: Putting out the Fire of Inflammation Bo-Zong Shao,1,4 Shu-Ling Wang,2 Peng Pan,2 Jun Yao,3 Kai Wu,1 Zhao-Shen Li,2,4 Yu Bai,2,4 and En-Qiang Linghu1,4
Abstract— Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, comprised of ulcerative colitis and Crohn’s disease. Among the complicated pathogenic factors of IBD, the overaction of inflammatory and immune reaction serves as an important factor. Inflammasome is a form of innate immunity as well as inflammation. Among all kinds of inflammasomes, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is the most studied one, and has been revealed to be involved in the pathogenesis and progression of IBD. Here, in this review, the association between the NLRP3 inflammasome and IBD will be discussed. Furthermore, several NLRP3 inflammasome inhibitors which have been demonstrated to be effective in the alleviation of IBD will be described in this review. KEY WORDS: inflammatory bowel disease; NLRP3 inflammasome; ulcerative colitis; Crohn’s disease; inflammation; autophagy.
INTRODUCTION The intestinal tract is the largest organ for digesting food and absorbing nutrients isolated from the intestinal contents [1, 2]. During the processes of digesting and absorbing, the intestinal mucosal barrier, composed by mucosal barrier layer, intestinal epithelial cells, and other inflammatory and immune cells, acts as important components in the intestinal defense system, preventing the invasion of external pathogens [3–5]. However, under certain conditions, the inflammatory and immune responses in the gut are over-reacted, leading to the damage of the intestinal
Bo-Zong Shao, Shu-Ling Wang, Peng Pan and Jun Yao contributed equally to this work. 1
Department of Gastroenterology, General Hospital of the Chinese People’s Liberation Army, Beijing, China 2 Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China 3 Department of Gastroenterology, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China
mucosal barrier and disturbance of intestinal bacterial homeostasis [6–9]. Consequently, such abnormalities in the gut may lead to the pathogenesis and progression of inflammatory bowel disease (IBD), recognized as a group of intestinal disorders with chronic and recurrent characteristics [10, 11]. IBD is composed of two members, namely ulcerative colitis and Crohn’s disease. Among multiple pathogenic factors for IBD, the over-activation of intestinal inflammatory and immune reaction has been regarded as one of the vital causes in the onset and development of IBD [12–15]. As a result, suppressing the over-activated intestinal inflammation serves as an effective and promising strategy in the treatment of IBD. Inflammasome belongs to a component of innate immunity, which is also a form of inflammation, functioning in protecting organisms from the invasion
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