IL-12 acts directly on DC to promote nuclear localization of NF-kappaB and primes DC for IL-12 production.
We analyzed the expression of an IL-12 receptor by fresh dendritic cells (DC) and a DC line. Using RT-PCR, RNAse protection, and electrophoretic mobility shift assay analysis, we found that DC possess an IL-12 receptor with beta1 subunit (downstream box 1)-related differences from that on T cells. IL-12 signaling through this receptor involved members of the NF-KB but not STAT family. The unique properties of the IL-12 receptor on DC, characterized by a single class of binding sites with a Kd of about 325 pM, may underlie rather unique effects, such as IFNgamma-independent augmentation of class II antigen expression and priming for LPS-induced production of IL-12.
Department of Experimental Medicine, University of Perugia, Italy.
U
U
Grohmann
M L
ML
Belladonna
R
R
Bianchi
C
C
Orabona
E
E
Ayroldi
M C
MC
Fioretti
P
P
Puccetti
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects; D018664:Interleukin-12 / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000235:genetics; D053707:Receptors, Interleukin-12; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C508440:Il12rb1 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D004247:DNA