Human microglial cells express a functional IL-12 receptor and produce IL-12 following IL-12 stimulation.
Microglial cells (MC) are IL-12 producers in the central nervous system. Here, we found that IL-12 receptor subunits beta1 and beta2 were both constitutively expressed, and up-regulated by IFN-gamma, in human primary MC. IL-12p70, after binding to its receptor, is internalized into vesicles that qualify as early endosomes as indicated by intracellular colocalization with transferrin. IL-12 induced tyrosine phosphorylation and nuclear translocation of STAT4. IL-12 signaling in human MC also involved members of the NFkappaB family. IL-12p70 and, more effectively, the combination of IL-12p70 and IFN-gamma, induced IL-12p40 mRNA expression and bioactive IL-12p70 production. Human MC, thus, express a functional IL-12 receptor and produce bioactive IL-12 following IL-12 stimulation.
Taoufik
Y
Y
INSERM E-0109, Faculté de Médecine Paris XI, Le Kremlin-Bicêtre, France. yassine.taoufik@kb.u-psud.fr
de Goër de Herve
M G
MG
Giron-Michel
J
J
Durali
D
D
Cazes
E
E
Tardieu
M
M
Azzarone
B
B
Delfraissy
J F
JF
D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis* / Q000235:genetics; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; C508438:IL12RB1 protein, human; C508439:IL12RB2 protein, human; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D014443:Tyrosine; D007371:Interferon-gamma