Abstract
Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4+T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.
Highlights
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by inflammation in the large and/or small intestine associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and various microbial products [1, 2]
The acute intestinal inflammation can be induced by DSS in the T cellindependent condition [10], the adaptive immune responses mediated by Th2 cell play a needful role in the pathogenesis of dextran sulphate sodium- (DSS-)induced acute colitis [11]
This construct was transformed into Escherichia coli strain BL21DE3, and the expression of recombinant mouse IL-33 protein (rIL-33) was induced by isopropyl-β-dthiogalactoside and purified by using 6 × His-Tagged Protein Purification Kit (Beijing CoWin Biotech, Beijing, China), followed by ToxinEraser Endotoxin Removal Kit (GenScript, Nanjing, China) to remove any endotoxin that might have come from the host cells
Summary
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by inflammation in the large and/or small intestine associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and various microbial products [1, 2]. We used to think that the responding T cells exhibit a T-helper (Th) cell type 1 phenotype capable of producing IFN-γ in CD [3], whereas Th2 cytokine, such as IL-4, IL-5, or IL-13, is closely associated with UC [4] In addition to these major immune responses associated with CD and UC, Th17, which mainly produces IL-17A, has been linked to pathogenesis of IBD recently [5, 6]. A number of recent studies have suggested that IL-33 attenuates the development and perpetuation of chronic intestinal inflammation [25, 29] These findings have been replicated in the trinitrobenzene-sulfonic-acid- (TNBS-) induced colitis model [30]. We used DSS-induced acute colitis (a representative colitis model for UC) in mice to elucidate the influence of IL-33 in the development of inflammatory condition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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
