We further demonstrated that GSK2256294, a clinical EPHX2i, reduced the production of IL2, IL12p70, IL10 and TNFα in both ulcerative colitis and Crohn's disease patient-derived explant cultures.
According to the results, we hypothesize that the elevated level of IL-2+ and IL-21+ T cells and a positive correlation between IL-21+ cells with CAI in UC patients may contribute to the pathogenesis of disease.
In addition to the IL2/IL21 locus, we observed association of the TT genotype of SNP rs1545620 in MYO9B with UC (P = 0.0169; OR = 0.29, 95% CI 0.11-0.78) and association of rs17375018 in IL23R with pancolitis in Chinese UC patients (P = 0.002; OR = 2.38, 95% CI 1.41-4.02).
Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease.
Mice deficient in both interleukin-2 and beta 2-microglobulin expression (Beta 2mullnull x IL-2null mice) develop an inflammatory disease of the colon resembling ulcerative colitis.
The TDT showed some distortion of allelic transmission for the IL-2 polymorphism in the UC group, but this did not reach statistical significance (P = 0.09).
In the case of interleukin-2 knockout mice, the lesion restricted to the colon, is virtually identical to ulcerative colitis in humans, and is initiated by the normal bacterial flora.
Accordingly, proliferative responses of LPL-T in patients with Crohn's disease and ulcerative colitis to stimulation with CD3 MoAb plus IL-2 were examined and compared with controls.
A sensitive reverse haemolytic plaque assay to detect lymphokine-secreting T cells, and Northern blot analysis to detect expression of lymphokine messenger RNA (mRNA) were used to study interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production in the mucosa of children with Crohn's disease or ulcerative colitis (UC), and in histologically normal mucosa from patients without inflammatory bowel disease.