Distinct differences in tachykinin gene expression in ulcerative colitis, Crohn’s disease and diverticular disease: a role for hemokinin‐1?

Abstract

In the intestine, the tachykinins substance P (SP) and neurokinin A (NKA) are found in neurons and have key roles in motility, secretion, and immune functions. A new tachykinin, hemokinin (HK-1), has been identified in non-neuronal cells in recent years and its role in intestinal inflammation is unclear. We aimed to examine the expression of genes encoding tachykinin peptides and receptors in colon from patients with ulcerative colitis (UC), Crohn's disease (CD), and acute diverticular disease (DD). Human colon segments were dissected into mucosa and muscle, and evaluated for tachykinin and tachykinin receptor gene expression by real-time PCR. In UC mucosa, the TAC4 gene (encoding HK-1) was 10-fold more abundant than in control mucosa (P < 0.01). Similarly, TAC1 (encoding SP and NKA) and TACR1 (encoding NK1 receptor) displayed 6-fold and 12-fold upregulation, respectively, in UC mucosa, but no change occurred in UC muscle. In contrast to UC, no difference was observed for any tachykinin genes in CD mucosa. In CD muscle, expression of TAC1 (P < 0.01), TAC4 and TACR1 (both P < 0.05) were moderately upregulated. In DD, there was a decrease in TACR1 (P < 0.05), and TACR2 (encoding NK2 receptor, P < 0.0001) in muscle compared with control. Histological staining showed increased collagen fibers between muscle bundles in DD smooth muscle. We provide evidence for the first time that HK-1, like SP, may be involved in the pathophysiology of inflammatory bowel disease. Distinctly different expression patterns of tachykinin-related genes occur in UC, CD and DD.