Evidence for the in vivo role of class II transactivator in basal and IFN-gamma induced class II expression in mouse tissue.
The class II transactivator (CIITA) is a protein that induces the transcription of MHC class II genes. We studied the expression of CIITA in vivo, comparing steady state levels of CIITA and class II mRNA in various mouse tissues. Many tissues in normal mice contained mRNA for CIITA, correlating with class II mRNA. The basal expression of CIITA and class II mRNA in mice with disrupted IFN-gamma genes (GKO mice) was similar to that in wild-type mice. Injection of rIFN-gamma strongly induced CIITA and class II mRNA: CIITA mRNA increased at 2 hr and declined to baseline by 48 hr, whereas class II mRNA increased at 24 hr and returned to baseline at 7 days. Proinflammatory stimuli that induce IFN-gamma production (allogeneic cells and LPS) induce CIITA and class II expression in wild-type mice, but not in GKO mice. CIITA induction by IFN-gamma was partially sensitive to cycloheximide, suggesting that another protein is required for CIITA induction. The data suggest that CIITA is a major regulator of basal and induced class II expression in vivo.
Ramassar
V
V
Department of Medicine, Division of Nephrology and Immunology, University of Alberta, Edmonton, Canada.
Goes
N
N
Hobart
M
M
Halloran
P F
PF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D001667:Binding, Competitive; D003513:Cycloheximide / Q000494:pharmacology; D005784:Gene Amplification; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000493:pharmacokinetics / Q000502:physiology*
D000906:Antibodies; D008070:Lipopolysaccharides; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma; D003513:Cycloheximide; D012194:RNA-Directed DNA Polymerase