Colonic epithelial cells are a major site of macrophage inflammatory protein 3α (MIP-3α) production in normal colon and inflammatory bowel disease

Background and aim: Macrophage inflammatory protein 3alpha (MIP-3alpha) is a recently described lymphocyte directed C-C chemokine expressed predominately at extralymphoid sites, including the intestine. The aim of this study was to determine whether colonic epithelial cells produce MIP-3alpha and whether its expression is upregulated in inflammatory bowel disease. Methods and results: We found that interleukin 10 and tumour necrosis factor a dose dependently stimulated MIP-3alpha production in Caco-2 and HT-29 intestinal epithelial cells. In cytokine treated Caco-2 and HT-29 cells, a significant increase in MIP-3alpha protein production was observed after three hours and continued for at least 24 hours. Analysis of colonic tissues by quantitative real time polymerase chain reaction and ELISA revealed significantly elevated MIP-3alpha mRNA levels (7.9-fold; p<0.05) and Protein levels (8.9-fold; p<0.05) in Crohn's disease compared with controls or ulcerative colitis. MIP-3a immunoreactivity in normal colon and inflammatory bowel disease was principally associated with crypt and surface epithelial cells. Moreover, MIP-3alpha protein levels were elevated in primary epithelial cells isolated from patients with inflammatory bowel disease. Conclusions: These findings indicate that increased enterocyte MIP-3alpha production may play an important role in lymphocyte activation and recruitment to the colonic epithelium in Crohn's disease and ulcerative colitis.