| First Author | Siegmund B | Year | 2004 |
| Journal | Eur J Immunol | Volume | 34 |
| Issue | 9 | Pages | 2356-64 |
| PubMed ID | 15307168 | Mgi Jnum | J:91767 |
| Mgi Id | MGI:3050719 | Doi | 10.1002/eji.200425124 |
| Citation | Siegmund B, et al. (2004) Frontline: Interferon regulatory factor-1 as a protective gene in intestinal inflammation: role of TCR gamma delta T cells and interleukin-18-binding protein. Eur J Immunol 34(9):2356-64 |
| abstractText | 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 inthe anti-inflammatory effects of IRF-1.See accompanying article http://dx.doi.org/10.1002/eji.200425351 |
