DIFFERENTIAL IN-SITU EXPRESSION OF THE GENES ENCODING THE CHEMOKINES MCP-1 AND RANTES IN HUMAN INFLAMMATORY BOWEL-DISEASE

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of l eukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 pa tients with inflammatory bowel disease (IBD) and seven control patient s by use of S-35-labelled antisense RNA probes. MCP-1 and RANTES trans cripts were generally increased in the intestinal mucosa of patients w ith IBD compared with controls. Whereas MCP-1 gene expression in the m ucosa 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 abu ndant in vessel-associated cells, such as endothelial cells, medial sm ooth muscle cells, and intraluminal cells; in smooth muscle cells of t he intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-l-expressing ce lls was observed in tissue specimens from patients with IBD, in endoth elial cells of venules, and in cells present in the lumen of intestina l vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle c ells and myenteric plexus cells appeared to be comparable in control a nd diseased intestines. The increased number of MCP-1 and RANTES mRNA- expressing cells in mucosa from patients,vith IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Fur thermore, 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.