Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

Angela Dahlberg, Mark R. Auble, Thomas M Petro

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-β than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-γ/LPS, but not IFN-γ alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV.

Original languageEnglish (US)
Pages (from-to)422-432
Number of pages11
JournalVirology
Volume353
Issue number2
DOIs
StatePublished - Sep 30 2006

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Theilovirus
Virus Diseases
Interleukin-12
Macrophages
Demyelinating Diseases
Autoimmune Diseases
Interleukin-23
Infection

Keywords

  • B10.S
  • IL-12
  • IRF-3
  • Macrophages
  • SJL/J
  • TLR3
  • TLR7
  • TMEV

ASJC Scopus subject areas

  • Virology

Cite this

Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3. / Dahlberg, Angela; Auble, Mark R.; Petro, Thomas M.

In: Virology, Vol. 353, No. 2, 30.09.2006, p. 422-432.

Research output: Contribution to journalArticle

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