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 μM. Cholera toxin, an activator of G(s), 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 μM. Dibutyryl cAMP (Bt₂cAMP) stimulated IL-6 secretion time-dependently up to 48 h. The effect of Bt₂cAMP on IL-6 secretion was dose-dependent in the range between 0.1 and 3 mM. N-[2-(p-bromocin-namylamino)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 Bt₂cAMP, 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.