Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis

<p>Abstract</p> <p>Background</p> <p>Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on <it>TLR2, TLR3</it>, and <it>TLR4 </it>participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of <it>TLR1 to 9 </it>in colonic mucosa of UC patients, according to disease activity.</p> <p>Methods</p> <p>Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of <it>TLR1 to 9, Tollip</it>, inflammatory cytokines <it>IL6 </it>and <it>TNF </it>were assessed by RT-qPCR with hydrolysis probes. Characterization of <it>TLR9 </it>protein expression was performed by Immunohistochemistry.</p> <p>Results</p> <p>Toll-like receptors <it>TLR8, TLR9</it>, and <it>IL6 </it>mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the <it>TLR2, TLR4, TLR8 </it>and <it>TLR9 </it>mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas <it>TLR5 </it>showed a trend (p = 0.06). <it>IL6 </it>and <it>TNF </it>mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, <it>IL6 </it>and <it>TNF </it>mRNA positively correlate with TLRs mRNA with the exception for <it>TLR3</it>, with stronger correlations for <it>TLR5, TLR8</it>, and <it>TLR9 </it>(p < 0.0001). <it>TLR9 </it>protein expression was mainly in the lamina propria infiltrate.</p> <p>Conclusions</p> <p>This study demonstrates that <it>TLR2, TLR4, TLR8</it>, and <it>TLR9 </it>expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.</p

Peroxisome Proliferator-Activated Receptors Family Is Involved in the Response to Treatment and Mild Clinical Course in Patients with Ulcerative Colitis

Background. PPARs play an important role in the regulation of intestinal inflammation. Methods. We included a total of 46 UC patients and 31 controls. The gene expression of PPARs was measured by RT-PCR and protein expression by immunohistochemistry. Results. PPARα gene expression was significantly decreased in patients with active UC compared with remission UC group (P=0.001) and controls (P=0.001). We found that low gene expression of PPARα in mucosa confers a higher risk of UC activity (P≤0.0001, OR = 22.6). We observed an increase of PPARα expression in patients with UC who were treated with 5-aminosalicylates compared with those who received any other combined therapy (P=0.03, OR = 0.08). PPARγ gene expression was decreased in the active UC group compared with UC in remission (P=0.001) and control group (P=0.001). An increased expression of PPARγ gene was associated with mild clinical course of the disease (P≤0.001, OR = 0.05). No gene expression of PPARβ/δ was found in the colonic mucosa from UC patients and controls. Conclusion. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and a mild clinical course of the disease