Sulfasalazine inhibits activation of nuclear factor-κB in patients with ulcerative colitis

Background: Although sulfasalazine is widely used to treat inflammatory bowel disease, its mechanisms of action remain unclear. Activation of transcription factor nuclear factor (NF)-kappa B, 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-kappa B 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-kappa B DNA binding activity, NF-kappa Bp65/I kappa B alpha 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-kappa B and high levels of the expression of interleukin (IL)-1 beta 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-kappa B and the expression of IL-1 beta mRNA and IL-8 mRNA while I kappa B alpha 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-kappa B activation, resulting in the downregulation of pro-inflammatory cytokine mRNA expression. (C) 2005 Blackwell Publishing Asia Pty Ltd.