title: Sulfasalazine inhibits activation of nuclear factor-kappaB in patients with ulcerative colitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. ganhuatian@hotmail.com
authors.forename: Hua-Tian
authors.initials: HT
authors.lastname: Gan
authors.forename: You-Qin
authors.initials: YQ
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001706:Biopsy; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005819:Genetic Markers / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012460:Sulfasalazine / Q000627:therapeutic use*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005819:Genetic Markers; D007378:Interleukins; D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D012460:Sulfasalazine; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human