Ulcerative Colitis: Chen YQ

Li Z, Zhang de K, Yi WQ, Ouyang Q, Chen YQ, Gan HT. · Department of Gastroenterology and Geriatric Medicine West China Hospital, Sichuan University, Chengdu, China. · Arch Med Res. · Pubmed #18996285 No free full text.

Abstract: BACKGROUND: Activation of nuclear factor-kappa B (NF-kappaB), which controls transcription of various proinflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). The aim of this study was to investigate if NF-kappaB p65 antisense oligonucleotides may affect the expression of NF-kappaB p65 and cytokines in lamina propria mononuclear cells (LPMCs) from patients with UC. METHODS: LPMCs, which were isolated from intestinal mucosal biopsy specimens from patients with UC, were cultured with or without NF-kappaB p65 antisense oligonucleotides, missense oligonucleotides and dexamethasone. NF-kappaB p65 expression was determined by Western blot analysis. The expression of cytokine mRNA was studied by reverse transcription-polymerase chain reaction (RT-PCR). Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: NF-kappaB p65 antisense oligonucleotides resulted in downregulation of NF-kappaB p65 expression, blocked the expression of IL-1beta mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1beta and IL-8. These effects were greater than those of dexamethasone in cultured LPMCs from patients with UC (p <0.05). CONCLUSIONS: Application of NF-kappaB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.

Gan HT, Chen YQ, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · J Gastroenterol Hepatol. · Pubmed #15955209 No free full text.

Abstract: BACKGROUND: Although sulfasalazine is widely used to treat inflammatory bowel disease, its mechanisms of action remain unclear. Activation of transcription factor nuclear factor (NF)-kappaB, which controls transcription of various pro-inflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease. The purpose of the present study was to determine whether sulfasalazine therapy affected NF-kappaB activation and the expression of pro-inflammatory cytokines in patients with ulcerative colitis. METHODS: A total of 38 patients with moderate ulcerative colitis were investigated. Twenty-one patients received sulfasalazine. Seventeen patients did not receive any medication. Biopsy specimens were obtained from inflamed mucosa and analyzed for NF-kappaB DNA binding activity, NF-kappaBp65/IkappaBalpha protein expression and the levels of pro-inflammatory cytokine mRNA using electrophoretic mobility shift assay, western blot analysis, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. RESULTS: Increased activation of NF-kappaB and high levels of the expression of interleukin (IL)-1beta mRNA and IL-8 mRNA were detected in biopsy specimens from patients with ulcerative colitis. Therapeutic administration of sulfasalazine effectively downregulated the activation of NF-kappaB and the expression of IL-1beta mRNA and IL-8 mRNA while IkappaBalpha levels were stable. CONCLUSION: The therapeutic benefits for ulcerative colitis of sulfasalazine might at least in part be attributed to its ability to inhibit NF-kappaB activation, resulting in the downregulation of pro-inflammatory cytokine mRNA expression.