Suppression of interleukin-1 alpha production by protein kinase C activators in human vascular endothelial cells.
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)
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
M
M
Watanabe
Y
Y
Kawase
J
J
Tanabe
K R
KR
Min
S
S
Mue
K
K
Ohuchi
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000470:Alkaloids / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008235:Lyngbya Toxins / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000470:Alkaloids; D007375:Interleukin-1; D007546:Isoquinolines; D008070:Lipopolysaccharides; D008235:Lyngbya Toxins; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; C022176:teleocidins; C006610:aplysiatoxin; D015121:6-Ketoprostaglandin F1 alpha; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate