Retinoic acid suppresses interleukin-6 synthesis induced by prostaglandins in osteoblasts.
We previously reported that prostaglandin E1 (PGE1) induces the synthesis of interleukin-6 (IL-6) via cAMP production in osteoblast-like MC3T3-E1 cells, and that, on the other hand, prostaglandin F2alpha (PGF2alpha) stimulates IL-6 synthesis via activation of protein kinase C. In the present study, we examined the effect of retinoic acid on IL-6 synthesis induced by these two prostaglandins in MC3T3-E1 cells. Retinoic acid inhibited the IL-6 synthesis induced by PGF2alpha or PGE1 in a dose-dependent manner in the range between 0.1 and 10 nM. Retinoic acid also suppressed the IL-6 synthesis stimulated by 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera toxin, forskolin or dibutyryl cAMP was inhibited by retinoic acid. However, retinoic acid had little effect on the IL-6 synthesis induced by interleukin-1. These results indicate that retinoic acid inhibits IL-6 synthesis induced by prostaglandins in osteoblasts as follows: the inhibitory effect on the PGE1-induced IL-6 synthesis is exerted at a point downstream from cAMP, and the inhibitory effect on the PGF2alpha-induced IL-6 synthesis is exerted at a point downstream from protein kinase C.
Kozawa
O
O
Department of Pharmacology, Gifu University School of Medicine, Japan.
Tokuda
H
H
Kaida
T
T
Matsuno
H
H
Uematsu
T
T
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010006:Osteoblasts / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
D000527:Alprostadil; D003994:Bucladesine; D002273:Carcinogens; D002772:Cholera Toxin; D005576:Colforsin; D015237:Dinoprost; D005343:Fibrinolytic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D007641:Keratolytic Agents; D010120:Oxytocics; D011453:Prostaglandins; D013755:Tetradecanoylphorbol Acetate; D014212:Tretinoin; D000093242:Interleukin-6 Inhibitors