Article: article from journal or magazin.
Frontline: interferon regulatory factor-1 as a protective gene in intestinal inflammation: role of TCR gamma delta T cells and interleukin-18-binding protein.
European Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
The transcription factor IFN regulatory factor-1 (IRF-1) regulates production and activity of many inflammatory mediators and cells. Here, we investigated the role of IRF-1 in intestinal inflammation using clinical and histologic scores; inflammatory mediators were also measured in colonic tissue. Dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) was administered to wild-type (WT) or IRF-1 knockout (KO) mice. DSS or TNBS led to a dramatic increase in lethality and colitis severity in IRF-1 KO compared with WT mice. Reduced levels of IFN-gamma and IL-18-binding protein (IL-18BP) were observed in the colon of IRF-1 KO mice, whereas levels of inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated STAT-3, chemokines, TNF-alpha, IL-1beta, IL-15, and IL-18 were not significantly changed. Intestinal inflammation was not altered in IFN-gamma KO mice or in WT mice given neutralizing anti-IFN-gamma antibodies, but was increased in mice lacking TCR gamma delta lymphocytes, a population significantly decreased in the intestine of IRF-1-deficient mice. Administration of IL-18BP reversed the increased susceptibility of IRF-1 KO mice to DSS. These results suggest a protective role for IRF-1 in intestinal inflammation, with a possible anti-inflammatory and/or restorative role. IL-18BP and TCR gamma delta cells appear to be critical factors in the anti-inflammatory effects of IRF-1.
Animals, Colitis/etiology, DNA-Binding Proteins/genetics, DNA-Binding Proteins/physiology, Female, Glycoproteins/physiology, Intercellular Signaling Peptides and Proteins, Interferon Regulatory Factor-1, Interferon-gamma/physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphoproteins/genetics, Phosphoproteins/physiology, Receptors, Antigen, T-Cell, gamma-delta/physiology, T-Lymphocytes/physiology
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