Upregulation of the transient receptor potential vanilloid 1 in colonic epithelium of patients with active inflammatory bowel disease

Abstract

Transient receptor potential vanilloid 1 (TRPV1), the receptor of capsaicin, is a nonselective cation channel that is highly permeable to Ca²⁺. TRPV1 is involved in the activation of immune cells and plays a role in the pathogenesis of experimental colitis. The expression of TRPV1 in colonic epithelium and its correlation with inflammatory bowel disease (IBD) are poorly understood. In this study, colonic biopsies were taken from 60 patients with active inflammatory bowel disease, including 30 patients with ulcerative colitis (UC) and 30 patients with Crohn's disease (CD), and 30 healthy controls. Disease activity was assessed according to the Mayo score, Crohn's disease activity index (CDAI) score, and the level of C-reactive protein (CRP). The severity of histological inflammation was graded using a scoring system that was previously described. For immunohistochemical staining, sections were incubated with a polyclonal anti-TRPV1 antibody. Next, image analysis was performed to obtain an integrated option density (IOD) value to evaluate TRPV1 immunoreactivity of five random fields per section, which was 60973±29112 for the UC group, 61942±32083 for the CD group, and 35154±21293 for the control group. Our data showed that TRPV1 expression was significantly upregulated in colonic epithelium of IBD patients compared with controls (P<0.001). In addition, no significant differences were observed in TRPV1 expression between UC and CD groups (P>0.05). Although TRPV1 immunoreactivity was highly expressed on epithelial cells and infiltrating inflammatory cells in colonic biopsies of active IBD patients, TRPV1 expression did not significantly correlate with disease severity (P>0.05). Therefore, our findings suggested a crucial role of TRPV1 in inflammatory bowel disease, and indicated that further studies are clearly warranted to determine whether TRPV1 is a potential target for therapy.

Keywords: Capsaicin; TRPV1; immunohistochemistry; inflammatory bowel disease.

Figure 1

A, B. The expression of TRPV1 in colonic mucosa of controls. Weak and scattered immunostaining was found, localized to the basolateral membrane of epithelial cells, while most of the interstitial cells of lamina propria were negative for TRPV1 immunostaining. C, D. The expression of TRPV1 in colonic mucosa of patients with ulcerative colitis. Both epithelial cells and infiltrated inflammatory cells showed strong TRPV1 immunostaining (a. colonic epithelial cells; b. infiltrated inflammatory cells). E, F. The expression of TRPV1 in colonic mucosa of patients with Crohn’s disease. Strong TRPV1 immunostaining was observed on epithelial cells and infiltrated inflammatory cells (a. colonic epithelial cells; b. infiltrated inflammatory cells).

Figure 2

The expression of TRPV1 significantly increased in the colonic mucosa of patients with IBD compared with normal mucosa from non-IBD controls (P<0.001). No significant differences was observed between the UC and CD group (P>0.5).

Figure 3

A. Scatter plot showed no significant correlation between TRPV1 expression and the Mayo score in the UC group (r=-0.316, P=0.089). B. Scatter plot showed no significant correlation between TRPV1 expression and CDAI score in the CD group (r=-0.274, P=0.143). C. Scatter plot showed no significant correlation between TRPV1 expression and CRP (r=-0.110, P=0.402).

Figure 4

A. Scatter plot showed no significant correlation between TRPV1 expression and histological inflammation score in UC group (P>0.5). B. Scatter plot showed no significant correlation between TRPV1 expression and histological inflammation score in CD group (P>0.05).