title: Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis.
abstract: OBJECTIVE
  Previous studies suggest the homeostasis between acquisition of tolerance to the indigenous microflora and protective immune responses appears to be disrupted in inflammatory bowel disease (IBD). Some experimental studies indicate peroxisome proliferator-activated receptor γ (PPARγ) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll-like receptor (TLR)-4 can regulate expression of PPARγ in colonic epithelial cells. We attempted to demonstrate whether the functional imbalance between TLRs and PPARγ could lead to the onset and some polymorphisms of those genes could contribute to susceptibility to IBD.
  
  
  METHODS
  RT-PCR analysis were performed to detect TLR4 and PPARγ mRNA associated with those of P65 of NFκB, TNFα, MyD88, NOD2/CARD15, TLR-2,5,9, in the diseased colonic mucosa in ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 7) compared with normal controls (n = 18). Consequently, we genotyped UC (n = 29) and CD (n = 10) compared with normal controls (n = 134) for the prevalence of suspicious mutations.
  
  
  RESULTS
  In a subset of UC patients who were revealed to carry PPARγ Pro12Ala mutation later, impaired expression of normal PPARγ mRNA was noted in the diseased mucosa accompanied with upregulations of MyD88 TLR-4, 5, 9, P65 and TNFα in mRNA levels. The prevalence of PPARγ Pro12Ala mutation was more frequently found in UC patients compared with CD patients and normal controls (P < 0.05).
  
  
  CONCLUSIONS
  These findings suggested that imbalances between TLRs and PPARγ in response to luminal bacteria could lead to colonic inflammation in some UC patients. Alternative explanations will be needed for the onset of the rest of UC and CD.
authors.affiliation: Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kudo
authors.forename: Toru
authors.initials: T
authors.lastname: Fujii
authors.forename: Mariko
authors.initials: M
authors.lastname: Wada
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamashiro
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D009154:Mutation; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D017678:Sex Distribution; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4