Premium
Sulfasalazine inhibits activation of nuclear factor‐κB in patients with ulcerative colitis
Author(s) -
GAN HUATIAN,
CHEN YOUQIN,
OUYANG QIN
Publication year - 2005
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2005.03862.x
Subject(s) - sulfasalazine , ulcerative colitis , medicine , inflammatory bowel disease , cytokine , electrophoretic mobility shift assay , colitis , pathogenesis , proinflammatory cytokine , western blot , immunology , transcription factor , pathology , inflammation , biology , disease , gene , biochemistry
Background: Although sulfasalazine is widely used to treat inflammatory bowel disease, its mechanisms of action remain unclear. Activation of transcription factor nuclear factor (NF)‐κB, 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‐κB 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‐κB DNA binding activity, NF‐κBp65/IκBα 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‐κB and high levels of the expression of interleukin (IL)‐1β 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‐κB and the expression of IL‐1β mRNA and IL‐8 mRNA while IκBα 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‐κB activation, resulting in the downregulation of pro‐inflammatory cytokine mRNA expression.