title: A new transcription factor that regulates TNF-alpha gene expression, LITAF, is increased in intestinal tissues from patients with CD and UC.
abstract: BACKGROUND
  The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Recently, a new transcription factor termed LITAF (lipopolysaccharide-induced TNF-alpha factor) was shown to mediate TNF-alpha expression in human macrophages by direct binding to specific sequences in the promoter region of the TNF-alpha gene.
  
  
  METHODS
  In this report, we identified LITAF in resected ileal and colonic tissues from patients with CD and UC by immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis. LITAF expression in inflamed and noninflamed areas of the tissues was compared.
  
  
  RESULTS
  This is the first demonstration of LITAF, a newly discovered transcription factor that regulates TNF-alpha gene transcription in ileal and colonic tissues from patients with either CD or UC. LITAF immunostaining was localized to lamina propria macrophages and was markedly increased relative to tissues from controls without inflammatory bowel disease. In patients with CD, a 5-fold increase in LITAF mRNA was measurable in noninflamed colonic tissues compared with controls without inflammatory bowel disease. LITAF mRNA in tissues from inflamed areas of the colon was increased by an additional 60% compared with noninflamed tissues. In patients with UC, LITAF mRNA levels in colonic tissues resected from noninflamed areas were elevated 15-fold above nondisease controls, but they were not different in tissues resected from inflamed areas. Western blot analysis showed that in patients with CD, there was a marked increase in LITAF protein in inflamed areas compared with noninflamed areas. LITAF protein levels were not different between noninflamed and inflamed tissues obtained from patients with UC. TNF-alpha mRNA and protein levels paralleled LITAF. Similarly, in inflamed ileal tissues from patients with CD, LITAF is also localized to lamina propria macrophages. LITAF mRNA and LITAF protein were significantly increased in inflamed ileal tissues compared with noninflamed areas.
  
  
  CONCLUSIONS
  LITAF is readily detectable in ileal and colonic tissues from patients with either CD or UC, is significantly elevated above controls, and is localized to macrophages, a major source of TNF-alpha. These data provide strong evidence of a role for LITAF in the pathophysiological regulation of the TNF-alpha gene and underscore the potential value of anti-LITAF strategies in the clinical management of these diseases.
authors.affiliation: Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Stucchi
authors.forename: Karen
authors.initials: K
authors.lastname: Reed
authors.forename: Michael
authors.initials: M
authors.lastname: O'Brien
authors.forename: Sandra
authors.initials: S
authors.lastname: Cerda
authors.forename: Charles
authors.initials: C
authors.lastname: Andrews
authors.forename: Adam
authors.initials: A
authors.lastname: Gower
authors.forename: Kristen
authors.initials: K
authors.lastname: Bushell
authors.forename: Salomon
authors.initials: S
authors.lastname: Amar
authors.forename: Susan
authors.initials: S
authors.lastname: Leeman
authors.forename: James
authors.initials: J
authors.lastname: Becker
mesh_terms: D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; C118738:LITAF protein, human; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D012313:RNA