Prostaglandin E1 stimulates interleukin-6 secretion via protein kinase A in osteoblast-like cells.
We investigated the effect of prostaglandin E1 (PGE1) on the secretion of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells. PGE1, which induced cAMP accumulation, stimulated IL-6 secretion time-dependently up to 48 h. The stimulative effect of PGE1 was dose-dependent in the range between 10 nM and 10 microM. Cholera toxin, an activator of Gs, stimulated IL-6 secretion in MC3T3-E1 cells. Forskolin, which directly activates adenylate cyclase, significantly induced IL-6 secretion in a dose-dependent manner in the range between 1 and 50 microM. Dibutyryl cAMP (Bt2-cAMP) stimulated IL-6 secretion time-dependently up to 48 h. The effect of Bt2-cAMP on IL-6 secretion was dose-dependent in the range between 0.1 and 3 mM. N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide (H-89), a potent and selective inhibitor of protein kinase A, which suppressed the IL-6 secretion induced by forskolin or Bt2-cAMP, significantly inhibited the IL-6 secretion induced by PGE1. These results indicate that PGE1 stimulates IL-6 secretion via the activation of protein kinase A in osteoblast-like cells.
Watanabe-Tomita
Y
Y
First Department of Internal Medicine, Nagoya University, School of Medicine, Japan.
Suzuki
A
A
Oiso
Y
Y
Kozawa
O
O
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D015850:Interleukin-6; D007546:Isoquinolines; D013449:Sulfonamides; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000527:Alprostadil; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide