Characterization of chemokines and chemokine receptors in two murine models of inflammatory bowel disease: IL-10(-/-) mice and Rag-2(-/-) mice reconstituted with CD4(+)CD45RB(high) T cells

We used quantitative PCR to investigate the expression of chemokines and ch emokine receptors in two Th1-mediated murine models of inflammatory bowel d isease (IBD). First, mRNA levels encoding the chemokines MIG, RANTES, lymph otactin, MIP-3 alpha, TCA-3, TARC, MIP-3 beta, LIX, MCP-1 and MIP-1 beta an d the receptors CCR4, CCR6 and CCR2 were significantly increased in chronic ally inflamed colons of IL-10(-/-) mice when compared with wildtype mice. I nterestingly, reversal of colitis in IL-10(-/-) mice by anti-IL-12 mAb was accompanied by the inhibition in the expression of LIX, lymphotactin, MCP-1 , MIG, MIP-3 alpha, MIP-3 beta, TCA-3, CCR2 and CCR4, whereas the increased mRNA levels of MIP-1 beta, RANTES, TARC and CCR6 were unaffected. Second, to investigate which chemokines and receptors were up-regulated during the inductive phase of colitis, we employed the CD4(+)CD45RB(high) T cell trans fer model. At 4 and 8 weeks after reconstitution of Rag-2(-/-) mice the mRN A levels of IP-10, MCP-1, MDC, MIG, TARC, RANTES, CCR4 and CCR5 were signif icantly increased prior to the appearance of macroscopic lesions. Other che mokines and chemokine receptors were clearly associated with the acute phas e of the disease when lesions were evident. The sum of our studies with the se two models identifies chemokines that are expressed at constant levels, irrespective of inflammatory responses, and those that are specifically ass ociated with acute and/or chronic stages of Th1-driven colitis.