Dendritic cell (DC) regulation of natural killer T cells may be altered in Crohns disease inflammation: Loss of MHC class I-like CD1 molecules from mucosal dendritic cells

expression of TNBS colitis in mice. Methods: Samples were obtained from healthy and inflamed colonic mucosa from 28 IBD patients (14 CD, 14 UC) not receiving therapy, and from 19 non-IBD controls. TNBS colitis was induced in 57 Balb/c mice and compared with 20 control mice. P38 and JNK expression and activity were quantified in colonic specimens by western blot and kinase assays. A pilot investigation with 36 mice was used to determine optimal dose and mode of SB203580 administration. Subsequendy, a controlled study was performed using SB203580 given 30 minutes before and 18 hours after induction of TNBScolitis or a saline/ethanol control. Mice were sacrificed 2 days after induction. Colitis severity was quantified by survival rates, macroscopic and microscopic colitis scoring systems, and quantification of myeloperoxidase (MPO), TNF-a mRNA and IL-1 iB mRNA, and p38 and JNK activity. Results: p38 and JNK expression and activity were similar in all specimens from humans. In mice, p38 and JNK expression or activity did not increase following TNBS colitis induction. Treatment with 5B203580 had no therapeutic effect on macroscopic or microscopic inflammation, nor did it modify the levels of MPO, TNF-Ix mRNA or IL-I~ mRNA. SB203580 treatment was associated with a 30% reduction in p38 activity, but JNK activity was unchanged. Conclusion: We were unable to demonstrate any consistent role in IBD for p38 and JNK MAPKs in either humans or in animal models of IBD. These results suggest that the inflammatory cascades in IBD act independently of p38 and JNK MAPK signaling pathways.