Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), whereas ulcerative colitis is probably driven by the production of IL-13.
Taken together, these results suggest a potential role for ZIP8 in intestinal inflammation, induced by IFNγ in the intestinal epithelial compartment, and that perturbations in negative regulation of NF-κB by ZIP8 A391T may contribute to CD pathogenesis.
BT-11 significantly decreases interferon gamma positive (IFNγ+) and tumor necrosis factor alpha positive (TNFα+) cluster of differentiation 4 positive (CD4+) T cells and increases forkhead box P3 positive (FOXP3+) CD4+ T cells in colonic lamina propria mononuclear cells from patients with CD and patients with UC at concentrations of 0.01 µM when treated ex vivo.
We identified decreased expression of RNASET2 as a component of TL1A-mediated increase in production of IFNG and as a potential biomarker for patients with severe CD.
Elevated levels of the pro-inflammatory cytokine, interferon-gamma (IFNgamma), are believed to be prominently involved in the pathogenesis of Crohn disease.
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.
Peripheral T cells of UC and Crohn's disease (CD) patients were genotyped for rs1861494 and analyzed for allele-specific and IFNG promoter methylation.
Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC.
Expression of growth-related oncogene-alpha was increased in intestinal TB, while expression of interferon-gamma (IFN-) and TLR 4, 5 and 9 was increased in Crohn's disease.
Elevated levels of IL-4 (2.91-fold) and IL-13 (4.05-fold) mRNA were detected in the inflamed colon mucosa of patients with ulcerative colitis (UC), IFN-γ mRNA was upregulated (3.23-fold) in the inflamed colon mucosa of patients with Crohn's disease (CD), whereas upregulation of IL-17A and TL1A mRNA was present in the inflamed colon mucosa of patients with both CD and UC (IL-17A: 4.48-fold and 2.74-fold, TL1A: 3.19-fold and 3.22-fold, respectively) vs. control subjects.
The stimulatory effects of these cytokines on naive T cells in addition to a strongly synergistic action with IL-12 to trigger interferon-gamma production may contribute to the perpetuation of the inflammatory process in patients with CD.
We found that the frequency of IFN-γ- and IL-17-expressing CD4 T cells was significantly higher after stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL-4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation with CD bacteria.
Intestinal and mesenteric lymph node samples from 9 children who had undergone ileal resection for CD were examined for the presence of epithelioid-giant cell granulomas (EGCG) and Rantes and IFN-gamma messenger RNA (mRNA).
Besides gene-level CD association P-values, association with AI diseases was the strongest predictor, highlighting generalized mechanisms of inflammation, and the interferon-γ pathway particularly.
It has recently been suggested that Crohn's Disease (CD) is associated with an exaggerated T helper 1 cytokine response as manifest by increased production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma).
We studied markers in the genes for NRAMP1 and two mutations in the interferon-gamma receptor in relation to inflammatory bowel disease (IBD) in the following groups: 270 healthy individuals, 74 patients with Crohn's disease, 72 patients with ulcerative colitis, and 40 patients with primary sclerosing cholangitis.
Quantitative gene expression analysis, by real-time PCR, of IL-32, IL-1β, IL-10, TNF-α and IFN-γ was performed on ileal biopsies of 15 AS and 15 Crohn's disease (CD) patients and 10 healthy subjects (HSs).
Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively.