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

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 gamma (PPAR gamma) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll-like receptor (TLR)-4 can regulate expression of PPAR gamma in colonic epithelial cells. We attempted to demonstrate whether the functional imbalance between TLRs and PPAR gamma 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 PPAR gamma mRNA associated with those of P65 of NF kappa B, TNF alpha, 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 PPAR gamma Pro12Ala mutation later, impaired expression of normal PPAR gamma mRNA was noted in the diseased mucosa accompanied with upregulations of MyD88 TLR-4, 5, 9, P65 and TNF alpha in mRNA levels. The prevalence of PPAR gamma 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 PPAR gamma 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.