Flavonoids, but not protein kinase C inhibitors, prevent stress protein synthesis during erythrophagocytosis.

Erythrophagocytosis induces in monocytes-macrophages the synthesis of stress proteins including the classical heat shock proteins (HSPs) and heme oxygenase (HO). To evaluate the role of oxygen radicals in this induction, we used the antioxidant flavonoids quercetin and kaempferol. These compounds inhibited HSP and HO synthesis, the latter being more sensitive. Quercetin and kaempferol also are inhibitors of protein kinase C (PKC). In order to determine whether inhibition of stress protein synthesis by flavonoids was mediated by their antioxidant properties or by PKC inhibition, we also tested more specific PKC antagonists, staurosporine and H-7. Staurosporine (SS) and H-7 decreased the synthesis of HSP70 and HSP83 but had no effect on HO. These data suggest that (1) erythrophagocytosis-related oxygen radicals are involved in the induction of the stress response in phagocytic cells, (2) the induction of HSPs and HO is differentially regulated, and (3) the effects of flavonoids on HO are linked to their scavenging activity rather than to PKC modulation.