Human microglial cells express a functional IL-12 receptor and produce IL-12 following IL-12 stimulation

Abstract

Microglial cells (MC) are IL-12 producers in the central nervous system. Here, we found that IL-12 receptor subunits β1 and β2 were both constitutively expressed, and up-regulated by IFN-γ, 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 NFκB family. IL-12p70 and, more effectively, the combination of IL-12p70 and IFN-γ, 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.