Identification of protein kinase C isoforms involved in interferon-gamma-induced expression of inducible nitric oxide synthase in murine BV2 microglia.

摘要

Microglia are major inflammatory cells of the brain. It has been known that interferon-gamma (IFN-gamma) induces nitric oxide (NO)/inducible nitric oxide synthase (iNOS) in microglia, and that protein kinase C (PKC) mediates the action of IFN-gamma. In this study, we investigated isoforms of PKC that are involved in IFN-gamma-induced activation of microglia using BV2 murine microglial cells. NO release/iNOS expression in IFN-gamma -treated BV2 cells was reduced in the presence of PKC inhibitors (Go 6976 and BIM), and by long-term pre-treatment (48 h) of cells with phorbol-12-myristate-13-acetate (PMA) or thymeleatoxin. PMA depleted alpha, beta, delta, and varepsilon isoforms, and thymeleatoxin depleted alpha, beta, and varepsilon isoforms although gamma, eta, iota, lambda, theta, mu, and zeta were also detected in these cells. Furthermore, IFN-gamma phosphorylated alpha and varepsilon on their tyrosine residues. These results suggested that alpha and varepsilon could be the major PKC isoforms involved in signaling pathways of IFN-gamma to induce NO/iNOS expression in BV2 microglia.