Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers.

Abstract

The spontaneous induced release of interferon y (IFN y)

Requirement of Histone Deacetylase Activity for Signaling by STAT1

“…IFN␥ is secreted by lamina propria cells, and its levels are strongly up-regulated in the intestinal mucosa from patients with inflammatory bowel disease (IBD) (21)(22)(23)(24). Furthermore, elevated levels of STAT1, as well as the other STAT family members (STAT3, STAT5, and STAT6), were detected in the colonic mucosa of patients with ulcerative colitis and Crohn's disease (25).…”

“…We also present evidence that the inducible expression of STAT1, STAT2, and caspase-7 was not repressed by HDAC inhibitors, which demonstrates that IFN␥ induces the expression of STAT1, STAT2, and caspase-7 independently of functional STAT1 signaling. Signaling by IFN␥ is deregulated in several inflammatory diseases, including IBD (21)(22)(23)(24). Elevated levels of STAT1 or activation of STAT1 has been demonstrated in Crohn's disease, in ulcerative colitis, and in pouchitis (26,27).…”

Blocking Smad7 restores TGF-β1 signaling in chronic inflammatory bowel disease

“…All patients were receiving corticosteroids, although the indication for surgery was a chronic active course poorly responsive to medical treatment. Additional mucosal samples were taken during endoscopy from 11 patients with moderate-to-severe CD (median age, 18 years; range, [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. In all of these patients, the primary site of involvement of the disease was the terminal ileum and colon.…”

Reduced Intracellular T-Helper 1 Interferon-Gamma in Blood of Newly Diagnosed Children With Crohn's Disease and Age-Related Changes in Th1/Th2 Cytokine Profiles

“…In contrast, the levels of CD4 ϩ and Th2 cells did not differ between CD patients and controls. A number of studies have examined the expression of T cell cytokines in intestinal mucosa and found increased levels of IFN-␥ mRNA and frequencies of IFN-␥ producing T-cells in adult patients with IBD compared with controls (7,8,33). However, the only available study of young children with newly diagnosed untreated IBD, which used flow cytometric assay of blood lymphocytes as in our study, also found the median Th1% in CD patients (n ϭ 14) was lower than in healthy subjects (n ϭ 9).…”

“…First, most previous studies involved older patients with long-standing disease or patients undergoing various therapeutic interventions; therefore, the patterns of cytokine expression could be influenced by these factors. Second, as serum cytokine bioassays detect the cytokines from both lymphocytes and macrophages; the source of elevated Th1 cytokines cannot be specified (7,8). Using flow cytometric analysis of intracellular cytokines, Van Damme et al have examined different subtypes of colonic lamina propia lymphocytes from IBD patients and found no difference in the frequencies of IFN-␥ producing CD3 ϩ…”