Cytokine/chemokine messenger-RNA expression profiles in ulcerative colitis and Crohn's disease

Abstract

To define mediator profiles in inflamed and noninflamed areas in inflammatory bowel disease (IBD) we analyzed the expression of 35 messenger-RNAs (mRNAs) encoding cytokines, chemokines, and some related molecules in transmural gut tissues (n=138) from patients with ulcerative colitis (UC), Crohn's disease (CD), and inflammatory and normal controls by real-time quantitative reverse transcription polymerase chain reaction. Using sample collectives with a comparable degree of inflammation, most parameters investigated showed similarly increased mRNA expression levels in both active UC and CD. This included proinflammatory cytokines, but also interferon (IFN) gamma and several IFN-gamma inducible chemokines. Only macrophage inflammatory protein (MIP)-2alpha mRNA was expressed at higher levels in inflamed UC vs. CD. IH revealed that MIP-2alpha protein was produced mainly by intestinal epithelial cells. Importantly, in histologically noninflamed/inactive IBD samples mRNAs for several mediators were significantly enhanced, accompanied by elevated levels of migration-inhibition factor related protein (MRP) 14 transcripts. CD14 positive macrophages were found especially in noninflamed/inactive UC, many of which coexpressed the RFD-7 antigen. Our results indicate a substantial overlap in cytokine/chemokine mRNA expression in UC and CD. Elevated mediator expression is evident in noninflamed/inactive areas in both diseases. Local recruitment of MRP-14 positive leukocytes might contribute to this phenomenon. In inactive UC a phenotypically altered population of macrophages expressing CD14 might play an additional role.