Differential dysregulation of nitric oxide production in macrophages with targeted disruptions in IFN regulatory factor-1 and -2 genes

Cindy A. Salkowski, Sheila A. Barber, Gregory R. Detore, Stefanie N. Vogel

Research output: Contribution to journalArticle

Abstract

Recent studies have reported that IFN regulatory factor-1 (IRF-1) regulates nitric oxide (NO·) production in murine macrophages (Mφ). Since IRF-2 recognizes the same consensus sequence as IRF-1, we postulated that IRF-2 may also regulate NO·. Therefore, the ability of Mφ from IRF-2 homozygous (IRF-2(-/-)) and heterozygous (IRF-2(+/-)) knockout mice to produce NO· following LPS and/or IFN-γ stimulation was compared with the responses of IRF-1(-/-), IRF-1/(+/-), and C57BL/6(+/+) Mφ. IRF-2(-/-) Mφ produced less LPS-induced NO2- than IRF-2(+/-) or C57BL/6 Mφ. LPS and IFN- γ synergized to increase NO2- production from IRF-2(-/-) Mφ to ~50% of IRF-2(+/-) and C57BL/6 levels. Unexpectedly, IRF-2(-/-), IRF-2(+/-), and C57BL/6 Mφ produced comparable levels of inducible NO synthase mRNA in response to treatment with LPS and IFN-γ. IRF-1(-/-) Mφ produced barely detectable NO2- and low, but detectable, inducible NO· synthase mRNA in response to IFN-γ and LPS. These results indicate that IRF-1 and IRF-2 differ in their mechanism of NO· regulation and that IRF-2 regulates inducible NO· synthase post-transcriptionally.

Original languageEnglish (US)
Pages (from-to)3107-3110
Number of pages4
JournalJournal of Immunology
Volume156
Issue number9
StatePublished - May 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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