Transcription of the interferon gamma (IFN-gamma )-inducible chemokine Mig in IFN-gamma-deficient mice.
MuMig or Mig (murine monokine induced by interferon gamma) is a CXC chemokine whose induction is thought to be strictly dependent on interferon gamma (IFN-gamma). Here we have studied the expression of this chemokine gene in various organs of mice infected with vaccinia virus. We have employed animals deficient in either IFN-gamma (IFN-gamma(-/-)), or receptors for IFN-alpha/beta, IFN-gamma, or both IFN-alpha/beta and IFN-gamma (DR(-/-)) to dissect out the role of interferons in the induction of Mig during the host response to virus infection. Our data show that Mig mRNA and protein are expressed in organs of vaccinia virus-infected IFN-gamma(-/-) mice, albeit at lower levels compared with infected, wild-type animals. In the DR(-/-) mice and in IFN-gamma(-/-) mice treated with a neutralizing antibody to IFN-alpha/beta, Mig mRNA transcripts were completely absent. Our data indicate that, in vaccinia virus-infected IFN-gamma(-/-) mice, Mig mRNA expression is mediated through the interaction between IFN-gamma responsive element 1 (gammaRE-1) and IFN-alpha/beta-induced STAT-1 complex referred to as IFN-gamma response factor 2 (gammaRF-2). Further, our findings support the view that gammaRF-2 is the IFN-alpha/beta induced STAT-1 complex, IFN-alpha-activated factor. We have found that, in the absence of IFN-gamma, IFN-alpha/beta are able to induce Mig in response to a viral infection in vivo.
Mahalingam
S
S
School of Human and Biomedical Sciences, Division of Science and Design, University of Canberra, Canberra, ACT 2601, Australia.
Chaudhri
G
G
Tan
C L
CL
John
A
A
Foster
P S
PS
Karupiah
G
G
D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000378:metabolism
C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D004247:DNA