PROSTAGLANDIN E(1) STIMULATES INTERLEUKIN-6 SECRETION VIA PROTEIN-KINASE-A IN OSTEOBLAST-LIKE CELLS

We investigated the effect of prostaglandin E(1) (PGE(1)) on the secre tion of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells. PGE(1) , which induced cAMP accumulation, stimulated IL-6 secretion time-depe ndently up to 48 h. The stimulative effect: of PGE(1) was dose-depende nt in the range between 10 nM and 10 mu M. Cholera toxin, an activator of G(s), stimulated IL-6 secretion in MCT3-E1 cells. Forskolin, which directly activates adenylate cyclase, significantly induced IL-6 secr etion in a dose-dependent manner in the range between 1 and 50 mu M Di butyryl cAMP (Bt(2)cAMP) stimulated IL-6 secretion time-dependently up to 48 h. The effect of Bt(2)cAMP on IL-6 secretion was dose-dependent in the range between 0.1 and 3 mM. omocinnamylamino)ethyl]-5-isoquino line-sulfonamide (H-89), a potent: and selective inhibitor of protein kinase A, which suppressed the IL-6 secretion induced by forskolin or Bt(2)cAMP, significantly inhibited the IL-6 secretion induced by PGE(1 ). These results indicate chat PGE, stimulates IL-6 secretion via the activation of protein kinase A in osteoblast-like cells. Copyright (C) 1997 Elsevier Science Inc.