Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis.

Abstract

AIM:

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: Yo Aoyagi, Satoru Nagata, Takahiro Kudo, Toru Fujii, Mariko Wada, Yukihide Chiba, Yoshikazu Ohtsuka, Yuichiro Yamashiro, Toshiaki Shimizu, Toshifumi Ohkusa
• Journal: Pediatrics international : official journal of the Japan Pediatric Society (Pediatr Int) Vol. 52 Issue 5 Pg. 729-34 (Oct 2010) ISSN: 1442-200X [Electronic] Australia
• PMID: 20591056 (Publication Type: Journal Article)
• Copyright: © 2010 The Authors. Pediatrics International © 2010 Japan Pediatric Society.

Chemical References

• PPAR gamma
• RNA, Messenger
• Toll-Like Receptor 4

Topics

• Adolescent
• Age Distribution
• Case-Control Studies
• Child
• Child, Preschool
• Colitis, Ulcerative (epidemiology, genetics, pathology)
• Crohn Disease (epidemiology, genetics, pathology)
• Down-Regulation
• Female
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Humans
• Incidence
• Infant
• Intestinal Mucosa (pathology)
• Male
• Mutation
• PPAR gamma (genetics)
• Polymorphism, Genetic
• Prognosis
• RNA, Messenger (analysis)
• Reference Values
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Assessment
• Sex Distribution
• Signal Transduction
• Toll-Like Receptor 4 (genetics)