Differential usage of class II transactivator promoters PI and PIV during inflammation and injury in kidney.
Expression of class II transactivator (CIITA), the transcriptional regulator that controls all class II expression, is controlled in cell lines in vitro by three promoters: the dendritic cell promoter PI, the B cell promoter PIII, and the interferon-gamma (IFN-gamma)-inducible promoter, PIV. The authors examined the promoter usage in vivo in mouse kidney in the basal state and in response to IFN-gamma, endotoxin, allostimulation, and renal injury. Genetically modified mice were used to examine the dependency of each promoter on IFN-gamma and on the transcription factor interferon regulatory factor 1 (IRF-1). Usage of distinct CIITA promoters was monitored by real-time reverse transcriptase polymerase chain reaction (RT-PCR) using the unique sequences in the 5' end of the transcript from each promoter. Kidneys in both control mice and IFN-gamma knockouts expressed chiefly PI- and PIV-related products. Administration of recombinant IFN-gamma activated only promoter PIV. Endotoxin or allogeneic stimulation elevated the PIV-related mRNA, dependent on IFN-gamma and on IRF-1. Ischemic renal injury, however, increased the PI- and PIV-driven mRNA expression in wild-type but also in IFN-gamma-deficient mice. Thus the in vivo control of CIITA promoters in kidney is similar to that observed in vitro (i.e., basal-state usage of PI and IFN-gamma-dependent usage of PIV during inflammation), but it also shows additional levels of control: IFN-gamma-independent basal activity of PIV and IFN-gamma-independent induction of PIV during tissue injury.
Takeuchi
Oki
O
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Sims
Tasha N
TN
Takei
Yutaka
Y
Ramassar
Vido
V
Famulski
Konrad S
KS
Halloran
Philip F
PF
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D004195:Disease Models, Animal; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000502:physiology*; D007668:Kidney / Q000293:injuries* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009393:Nephritis / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; 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