Peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression is downregulated in patients with active ulcerative colitis

To the Editor: The peroxisome proliferator-activated receptor gamma (PPAR-γ) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor kappa B (NF-κB) activity. Impaired expression of PPAR-gamma in colonic epithelial cells in ulcerative colitis (UC) and increased expression in hypertrophic mesenteric adipose tissue in Crohn's disease (CD) have been reported.1 Recently, it has become controversial whether genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD).2,–4 However, this is the first study, to our best knowledge, with a larger sample that correlates the PPAR-γ gene expression negatively with disease activity in patients with UC. We measured the PPAR-γ gene expression from rectum biopsies of UC patients from September 2007 to August 2008. All individuals were divided into two groups: 1) active UC (n = 20), and 2) long-term UC remission (n = 20). All individuals were assessed for PPAR-γ and IL-6 mRNA transcripts levels relative to RPLP0 constitutive gene using real-time reverse-transcription polymerase chain reaction (RT-PCR) using LNA TaqMan probes from Roche (Nutley, NJ) in combination with target gene-specific primers PPAR-γ forward 5′-gacctgaaacttcaagagtaccaaa-3′ and reverse 5′-tgaggcttattgtagagctgagtc-3′; IL-6 5′-gcccagctatgaactccttct-3′, 5′-gaaggcagcaggcaacac-3′; and RPLP0 5′-acagggcgacctggaagt-3′, 5′-ggatctgctgcatctgctt-3′ for normalization. These results showed that PPAR-γ mRNA expression was decreased in rectal mucosa from patients with active UC compared to UC patients in remission (P = 0.02), as shown in Figure 1. We also found that PPAR-γ gene expression correlated negatively with endoscopic activity (r2 = −0.344, P = 0.04) Figure 2 and IL-6 expression (r2 = −0.439, P = 0.001) by Spearman correlation test. These findings confirmed the role of the PPAR-γ gene as a potential therapeutic target in UC, as suggested in a previous study that demonstrated the efficacy of rosiglitazone (thiazolidinedione agonist for PPAR-γ) in patients with mild to moderate UC activity.5 Gene expression of PPAR-γ in rectal mucosa from patients with UC (active/remission) and the constitutive gene RPL0. Negative correlation between PPAR-γ gene expression and endoscopic disease activity of UC. In conclusion, decreased gene expression of PPAR-γ was found from rectal biopsies in patients with active UC and its expression was negatively correlated with the severity of endoscopic disease activity. According to our results, the use of rosiglitazone could induce higher expression of PPAR-γ in the mucosa of the colon in order to decrease disease activity.