Enhanced expression and production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa.

Abstract

Peripheral blood monocytes are recruited to the inflamed mucosa of inflammatory bowel disease but the specific chemotactic signals responsible for their attraction are not known. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine with potent monocyte attracting and activating properties and the aim of this study was to examine its expression and production in inflammatory bowel disease. In situ hybridization demonstrated mRNA for MCP-1 in macrophages, some of which had been recently recruited from the circulation as demonstrated by their co-expression of the monocyte marker CD 14, as well as in smooth muscle and endothelial cells in inflamed mucosa. Immunohistochemical studies showed a corresponding distribution of MCP-1 protein production by macrophages, smooth muscle, and endothelial cells. By contrast minimal MCP-1 mRNA expression and protein were found in histologically normal mucosa. Macrophages isolated from surgically resected inflammatory bowel disease colons and examined by Northern analysis expressed MCP-1 mRNA significantly more frequently (15/24 vs. 0/19, P< 0.0001) than macrophages from histologically normal mucosa from colon cancer resections. Blood monocytes stimulated by lipopolysaccharide and treated with hydrocortisone, 5-aminosalicylic acid, or cyclosporin A showed reduced MCP-1 expression and production in the presence of these agents. This study demonstrates increased expression of MCP-1 mRNA and protein and cells of origin of MCP-1 in inflamed intestinal mucosa. Together with the demonstrated influence of therapeutic agents on monocyte MCP-1 production the findings suggest a role for MCP-1 in monocyte attraction to the mucosal lesion of inflammatory bowel disease.