Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease and ulcerative colitis.The exact etiology and pathology of IBD remain unknown.Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals.Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD,involving a wide range of molecules including cytokines.On the other hand,besides T helper(Th)1 and Th2 cell immune responses,other subsets of T cells,namely Th17 and regulatory T cells,are likely associated with disease progression.Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD.

Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells in vivo and in vitro

Background and Objective: S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on breast cancer, liver cancer and colon carcinoma. This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro, and the antitumor mechanisms. Methods: The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 μmol/(kg·day)], high concentration group [768 μmol/(kg·day)], and control group [normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP. Results: SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51± 149.27) mm3] and high concentration group [(444.32 ± 118.51) mm3] than in control group [(1018.22 ± 223.07) mm3] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment. Conclusions: SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.

Role of interleukin-22 in inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.