Abstract
Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice. Experimental colitis was induced by 2, 4, 6-trinitrobenzene sulfonic acid. After 7 days treatment with curcumin, its therapeutic effect was verified by decreased colonic weight, histological scores, and remitting pathological injury. Meanwhile, the levels of major histocompatibility complex class II and DC costimulatory molecules (CD83, CD28, B7-DC, CD40, CD40 L, and TLR2) were inhibited and followed the up-regulated levels of IL-4, IL-10, and IFN-γ, and down-regulated GM-CSF, IL-12p70, IL-15, IL-23, and TGF-β1. A key finding was that the phosphorylation of the three members (JAK2, STAT3, and STAT6) of the JAK/STAT/SOCS signaling pathway was inhibited, and the three downstream proteins (SOCS1, SOCS3, and PIAS3) from this pathway were highly expressed. In conclusion, curcumin suppressed the activation of DCs by modulating the JAK/STAT/SOCS signaling pathway to restore immunologic balance to effectively treat experimental colitis.
Highlights
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is an idiopathic disease characterized by chronic, relapsing, non-specific inflammatory reactions in the bowel
The body weights of the mice with colitis treated with 100 mg/kg curcumin and 300 mg/kg mesalazine were markedly higher than the TNBS group
Hyperaemia, and edema in local colonic mucosa in colitis mice without treatment were observed by visual assessment, they were ameliorated in colitis mice treated with curcumin and mesalazine (Figure 1B)
Summary
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is an idiopathic disease characterized by chronic, relapsing, non-specific inflammatory reactions in the bowel. DCs play the role of pivotal initiator in the abnormal immune response that relaxes mucosal vigilance against intestinal flora (Steinman, 2012; Al-Hassi et al, 2014). As the most powerful antigen-presenting cell, intestinal DCs distribute throughout the non-lymphoid and lymphoid tissues including lamina propria (LP), Peyer’s patches (PPs), Mesenteric lymph nodes (MLN), and so on. Intestinal DCs jointly maintain the dynamic balance in the gut between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Disruption of the balance can weaken mucosal immunogenicity against the pathogenic antigen and destroy the protection from commensal intestinal bacteria (Al-Hassi et al, 2014)
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