Abstract
When human umbilical endothelial cells (HUVEC) were incubated for 8h in the presence of TNFa (0.1 ng/ml), they produced cellassociated IL-1α. However, in the conditioned medium, no detectable amount of IL-lα was produced by the TNFa treatment. IL 1β also was not detected in the cells or in the conditioned medium. Combined treatment with TNFα (0.1ng/ml) and the protein kiase C (PKC) activator TPA (1 ng/ml) suppressed the TNFα-induced IL-1α production. A significant inhibition of the TNFα-induced IL-1α production was observed when HUVEC were pretreated with TPA (1 ng/ml) for 1 to 15 min. Other PKC activators such as aplysiatoxin (AT) or teleocidin (TC) at a concentration of 1 ng/ml also inhibited the TNFα-induced IL-1α production when HUVEC were pretreated for 15 min prior to the stimulation with TNFα. IL-1β (0.1 ng/ml) or lipopolysaccharide (LPS) (5μg/ml) also stimulated the cell-associated IL-1α production. Pretreatment with TPA, AT, or TC (1ng/ml) for 15 min suppressed the IL-1β-, or the LPS-induced IL-1α production. However, the inhibition of the TNFα-induced IL-1α production by TPA was not counteracted by pretreatment with the PKC inhibitor H-7 or staurosporine (SS) . TNFα stimulated PGI2 production, and pretreatment with TPA further increased PGI2 production. The TPA-induced PGI2 production was significantly suppressed by the pretreatment with H-7.
In conclusion, IL-1α production stimulated by TNFα, IL-1β, or LPS is inhibited by the PKC activators TPA, AT, or TC, but the inhibition of the IL-1α production might not be due to the activation of PKC, but by PKC-independent mechanisms.
