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. He re, we found that IL-12 receptor subunits beta1 and beta2 were both constit utively expressed, and up-regulated by IFN-gamma, in human primary MC. IL-1 2p70, after binding to its receptor, is internalized into vesicles that qua lify as early endosomes as indicated by intracellular colocalization with t ransferrin. IL-12 induced tyrosine phosphorylation and nuclear translocatio n of STAT4. IL-12 signaling in human MC also involved members of the NF kap paB family. IL-12p70 and, more effectively, the combination of IL-12p70 and IFN-gamma ,induced IL-12p40 mRNA expression and bioactive IL-12p70 product ion. Human MC, thus, express a functional IL-12 receptor and produce bioact ive IL-12 following IL-12 stimulation.