Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis

AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.

Effects of baicalin in CD4 + CD29 + T cell subsets of ulcerative colitis patients

AIM:To evaluate the role of baicalin in ulcerative colitis(UC) with regard to the CD4+CD29+ T helper cell,its surface markers and serum inflammatory cytokines.METHODS:Flow cytometry was used to detect the percentage of CD4+CD29+ cells in patients with UC.Real time polymerase chain reaction was used to detect expression of GATA-3,forkhead box P3,T-box expressed in T cells(T-bet),and retinoic acid-related orphan nuclear hormone receptor C(RORC).Western blotting was used to analyze expression of nuclear factor-κB(NF-κB) p65,phosphorylation of NF-κB(p-NF-κB) p65,STAT4,p-STAT4,STAT6 and p-STAT6.The concentrations of interferon-γ(IFN-γ),interleukin(IL)-4,IL-5,IL-6,IL-10 and TGF-β in serum were determined by ELISA assay.RESULTS:The percentages of CD4+CD29+ T cells were lower in treatment with 40 and 20 μmol/L baicalin than in the treatment of no baicalin.Treatment with 40 or 20 μmol/L baicalin significantly upregulated expression of IL-4,TGF-β1 and IL-10,increased p-STAT6/STAT6 ratio,but downregulated expression of IFN-γ,IL-5,IL-6,RORC,Foxp3 and T-bet,and decreased ratios of T-bet/GATA-3,p-STAT4/STAT4 and p-NF-κB/NF-κB compared to the treatment of no baicalin.CONCLUSION:The results indicate that baicalin regulates immune balance and relieves the ulcerative colitis-induced inflammation reaction by promoting proliferation of CD4+CD29+ cells and modulating immunosuppressive pathways.