Abstract

In human umbilical endothelial cells, treatment with tumor necrosis factor (TNF)-alpha stimulated the production of cell-associated interleukin (IL)-1 alpha. Combined treatment of human umbilical endothelial cells with TNF-alpha and the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA) suppressed the TNF-alpha-induced production of IL-1 alpha. However, concentrations of 6-keto-prostaglandin F1 alpha in the conditioned medium were increased to a greater extent by combined treatment with TNF-alpha and TPA than by single treatment with TNF-alpha or TPA. Pretreatment with TPA for 15 min was enough to suppress the TNF-alpha-induced IL-1 alpha production. Pretreatment for 15 min with other PKC activators such as aplysiatoxin or teleocidin, also inhibited the TNF-alpha-induced IL-1 alpha production. Stimulation of cell-associated IL-1 alpha production by IL-1 beta or lipopolysaccharide was also inhibited by pretreatment with the PKC activator TPA, aplysiatoxin or teleocidin. However, treatment with the protein kinase inhibitor 1-(5-isoquinoline-sulphonyl)-2- methylpiperazine dihydrochloride (H-7) did not block the inhibitory effect of TPA, aplysiatoxin or teleocidin on the cell-associated IL-1 alpha production stimulated by TNF-alpha, IL-1 beta or lipopolysaccharide, although the PKC activator-induced stimulation of 6-keto-prostaglandin F1 alpha production was counteracted by H-7 treatment. The present work indicates that the production of cell-associated IL-1 alpha stimulated by TNF-alpha, IL-1 beta or lipopolysaccharide is inhibited by treatment with TPA, aplysiatoxin or teleocidin.(ABSTRACT TRUNCATED AT 250 WORDS)