DIFFERENTIAL-EFFECTS OF PKC INHIBITORS ON GELATINASE-B AND INTERLEUKIN-6 PRODUCTION IN THE MOUSE MACROPHAGE

Pretreatment of LPS-induced RAW 264.7 cells with three PKC inhibitors suggests that induction of TNF-alpha, nitric oxide (NO), gelatinase B (Gel B) and IL-6 involves at least three distinct signalling pathways, We confirmed the PKC dependence of TNF-alpha and NO productions and f ound that Gel B was inhibited by Calphostin C (GAL), but potentiated b y staurosporine (STAR) and CGP 41 251, IL-6 production was stimulated by the three inhibitors, Our results indicate that up-regulation of Ge l B, TNF-alpha and NO seems to involve PKC at different levels, wherea s up-regulation of IL-6 production appears to be PKC-independent. Howe ver, IL-6 production in RAW 264.7 cells seems to be down-regulated by a PKC-dependent feedback mechanism.