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

Microglia are major inflammatory cells of the brain. It has been known that interferon-gamma (IFN-gamma) induces nitric oxide (NO)/inducible nitric ox ide synthase (iNOS) in microglia, and that protein kinase C (PKC) mediates the action of IFN-gamma. In this study, we investigated isoforms of PKC tha t are involved in IFN-gamma -induced activation of microglia using BV2 muri ne microglial cells. NO release/iNOS expression in IFN-gamma -treated BV2 c ells was reduced in the presence of PKC inhibitors (Go 6976 and BIM), and b y long-term pre-treatment (48 h) of cells with phorbol-12-myristate-13-acet ate (PMA) or thymeleatoxin. PMA depleted alpha, beta, delta, and epsilon is oforms, and thymeleatoxin depleted alpha, beta, and epsilon isoforms althou gh gamma, eta, iota, lambda, theta, mu, and zeta were also detected in thes e cells. Furthermore, IFN-gamma phosphorylated alpha and epsilon on their t yrosine residues. These results suggested that alpha and epsilon could be t he major PKC isoforms involved in signaling pathways of IFN-gamma to induce NO/iNOS expression in BV2 microglia. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.