In vivo class II transactivator expression in mice is induced by a non-interferon-gamma mechanism in response to local injury.
BACKGROUND
Tissue injury induces MHC class II expression, which could be important in the recognition of that tissue as an allograft. The class II transcriptional activator (CIITA) is the major regulator of basal and induced MHC class II expression and is essential for antigen presentation. The role of CIITA in the induction of class II by tissue injury is unknown. In this study, we examined CIITA induction in the course of acute ischemic or toxic renal injury in mice, including the role of interferon (IFN)-gamma and of the transcription factor, interferon regulatory factor (IRF)-1.


METHODS
Kidneys were injured by ischemia or by gentamicin toxicity and were then studied for changes in gene expression using Northern blot, reverse transcriptase-polymerase chain reaction, radioimmunoassay, and tissue staining. We compared wild-type (WT) mice to IFN-gamma knockout (GKO) or IRF-1 knockout mice.


RESULTS
Ischemic injury induced CIITA and class II expression in the kidney, in WT and GKO mice. Gentamicin injury also induced both CIITA and class II expression, independent of IFN-gamma, in WT and GKO mice. After ischemic injury, the induction of class II protein levels and CIITA and class II mRNA levels were induced, to a lesser degree, in IRF-1 knockout mice.


CONCLUSIONS
These data indicate that CIITA is induced by tissue injury, and probably accounts for class II induction during tissue injury. CIITA induction by injury is largely IFN-gamma independent but requires IRF-1. The similarities of the pattern of CIITA and class II induction in ischemic and toxic injury suggest that this is a stereotyped response of injured tissue and not a consequence of a particular mechanism of injury.
Sims
T N
TN
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Goes
N B
NB
Ramassar
V
V
Urmson
J
J
Halloran
P F
PF
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D005802:Genes, MHC Class II / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000502:physiology; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma