PMID: 12759457May 22, 2003Paper

Regulation of lipopolysaccharide sensitivity by IFN regulatory factor-2

The Journal of Immunology : Official Journal of the American Association of Immunologists
Natalia CuestaS N Vogel

Abstract

IFN regulatory factors (IRFs) are a family of transcription factors and include several members that regulate expression of pro- and anti-inflammatory genes. Mice with a targeted mutation in IRF-2 (IRF-2(-/-)) were studied after injection of LPS to evaluate the importance of IRF-2 in the regulation of endotoxicity. IRF-2(-/-) mice were highly refractory to LPS-induced lethality. Although hepatic TNF-alpha mRNA and circulating TNF-alpha were significantly elevated in LPS-challenged IRF-2(-/-) mice, levels of IL-1, IL-12, and IFN-gamma mRNA and protein, as well as IL-6 protein, were significantly lower than levels seen in LPS-challenged IRF-2(+/+) mice. IRF-2(-/-) mice were also more refractory to TNF-alpha challenge than were control mice, which was consistent with their diminished sensitivity to LPS, yet no significant difference in the mRNA expression of TNFRs was observed. IL-12R beta 2 mRNA levels from LPS-challenged IRF-2(-/-) mice were significantly different after 1, 6, and 8 h, suggesting that both diminished IL-12 and altered IL-12R expression contribute to the paucity of IFN-gamma produced. IRF-2 knockout mice also failed to sustain LPS-inducible levels of IRF-1 and IFN consensus sequence binding protein mRNA expressio...Continue Reading

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Citations

Nov 17, 2004·The Journal of Biological Chemistry·Justin MosteckiPaul B Rothman
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shinsuke TakiShigeaki Hida
Aug 17, 2006·The Journal of Biological Chemistry·Karen E ThomasStefanie N Vogel
Oct 13, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Vishwas D JoshiAlan S Cross
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leah E ColeStefanie N Vogel
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kari Ann ShireyStefanie N Vogel
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