Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease.

Abstract

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of leukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 patients with inflammatory bowel disease (IBD) and seven control patients by use of 35S-labelled antisense RNA probes. MCP-1 and RANTES transcripts were generally increased in the intestinal mucosa of patients with IBD, compared with controls. Whereas MCP-1 gene expression in the mucosa was restricted to the lamina propria, the gene coding for RANTES was expressed in intraepithelial lymphocytes and in the subepithelial lamina propria. Furthermore, MCP-1 mRNA, but not RANTES mRNA, was abundant in vessel-associated cells, such as endothelial cells, medial smooth muscle cells, and intraluminal cells; in smooth muscle cells of the intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-1-expressing cells was observed in tissue specimens from patients with IBD, in endothelial cells of venules, and in cells present in the lumen of intestinal vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle cells and myenteric plexus cells appeared to be comparable in control and diseased intestines. The increased number of MCP-1 and RANTES mRNA-expressing cells in mucosa from patients with IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Furthermore, the expression of the MCP-1 gene in vessel-associated cells may indicate its involvement in mechanisms regulating the adhesion of blood monocytes to endothelial cells.