Interleukin-1beta activates protein kinase C zeta in renal mesangial cells. Potential role in prostaglandin E2 up-regulation.
Protein kinase C (PKC) plays a role in signal transduction mediated by interleukin-1beta (IL-1beta) leading to the increase in prostaglandin E2 (PGE2) production. In the present study we suggest that there are at least two distinct PKC isotypes involved in the signaling mechanism. Staurosporine potentiated the effect of IL-1beta on coxII mRNA expression while calphostin C totally inhibited mRNA expression. The down-regulation of PKC by growing mesangial cells in the presence of phorbol 12-myristate 13-acetate for 24 h failed to modify the up-regulated response in PGE2 formation by IL-1beta. Furthermore, incubation of mesangial cells with IL-1beta causes translocation of PKCzeta from cytosol to a presumed membrane compartment, and this translocation phenomenon was not inhibited by incubating the cells with staurosporine but was inhibited with calphostin C. Gel retardation assays also demonstrated that staurosporine did not inhibit the IL-1beta-stimulated binding of nuclear extracts to the NFkappaB motif. In contrast, calphostin C inhibited binding to the kappaB motif in a dose-dependent manner. Finally, antisense oligonucleotides to PKCzeta partially inhibited the IL-1beta-induced PGE2 formation while control sense oligonucleotides were without effect. Taken together, these data suggest that PKCzeta is involved in the IL-1beta signaling responses.
Rzymkiewicz
D M
DM
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tetsuka
T
T
Daphna-Iken
D
D
Srivastava
S
S
Morrison
A R
AR
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D000099221:Protein Kinase C zeta
D000470:Alkaloids; D015232:Dinoprostone; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; D009281:Naphthalenes; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D000099221:Protein Kinase C zeta; C058819:calphostin C