Su1038 – Nod1 Deficient Gastric Stem Cells Fail to Differentiate to Parietal Cells and Cause Gastric Mucosal Atrophy

Background/aims: Inflammatory bowel disease (IBD) is a common disease associated with disorders of the innate and adaptive immune response.Sulforaphane (SFN), a phytochemical in broccoli sprouts, is well known to have anti-inflammatory, antitumor and antioxidative properties.regulates activation of the innate immune system.We aimed to determine Sulforaphane alleviates dextran sodium sulfate (DSS)-induced inflammation through miR-155a in macrophages, and evaluated the miR-155 related mechanisms of Sulforaphane effects on inflammation and polarization in macrophage.Experimental approach: C57BL/6 mice received DSS (2%) in drinking water with 30 mg/kg intraperitoneal (i.p.) injection either 0.9% normal saline (NS) as control or SFN for 7 days.RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or 20uM SFN for different hours to detect mRNA and protein levels.Results: We observed that SFN improved survival rate, reduced serum levels of pro-inflammatory cytokines IL-1β, IL-6, IL-18 and lowered histopathology scores after DSS-induced colitis.SFN affected the polarization status of intestinal macrophages evidenced by the increase of M2 marker Arg-1 and CD206 expression and the decrease of M1 marker iNOS and CD86 expression along with an increased Th2 cytokine IL-10 and decreased Th1 cytokine TNF-α in colon tissues and macrophages.Simultaneously, the inflammasome reduction of NLRP3 accompanied with increased polarization of phenotype resembling M2 macrophages.SFN markedly downregulated miR-155a in mouse colon and macrophages.As a target of miR-155, Quaking (QKI) is an inflammation-suppressor gene encoding a conserved RNA-binding protein.SFN reversed LPS-induced downregulation of QkI and QKI-dependent activated aryl hydrocarbon receptor (Ahr) expression both in mRNA and protein level.Introduction miR-155 expression in macrophages is induced by NF-kB and regulated by STATs.To identified how SFN regulates miR-155 in macrophages, We also analyzed NF-kB and STATs.SFN treatment inhibited phosphorylation of NF-κB p65 and STAT3 signal transducer, but enhanced STAT1 phosphorylation in LPS-induced macrophages.For further investigation, although Ahr was mediated by miR-155, Ahr responsed to negative feedback in NF-κB via form a complex with Stat1 and NF-κB p50 in LPS-induced macrophages after SFN stimulate.Ahr inhibited the NF-κB transcriptional activity and prolonged STAT1 activation.Conclusions: Our findings suggest that SFN protects DSS-induced colitis by switches macrophages polarization states in inflammation and defectives NLRP3 inflammasome activation.MiR-155 is a key regulator of Inhibiting proinflammatory for SFN treatment in macrophages.Ahr as a target of miR-155/QKI pathway also control S-491 AGA Abstracts and regulate Stat1/NF-κB/Ahr complex.Therefore, SFN might be a potential therapeutic agent for the treatment of IBD.