title: Triiodothyronine modulates interleukin-6 synthesis in osteoblasts: inhibitions in protein kinase A and C pathways.
abstract: In osteoblast-like MC3T3-E1 cells, we recently reported that PGE1 and PGF2alpha induce interleukin (IL)-6 synthesis via activation of protein kinase A and protein kinase C, respectively. Moreover, in the case of IL-1-induced IL-6 synthesis in these cells, we showed that protein kinase C activation by IL-1 limits the IL-6 synthesis. In the present study, we investigated the effect of T3 on IL-6 synthesis induced by these agonists in MC3T3-E1 cells. T3, which by itself had little effect on IL-6 synthesis, significantly reduced the IL-6 synthesis induced by PGE1 in a dose-dependent manner in the range between 10 pM and 10 nM. T3 also reduced PGE1-induced activation of protein kinase A. T3 inhibited the IL-6 synthesis induced by cholera toxin, an activator of Gs, or forskolin, which directly activates adenylate cyclase. However, T3 did not affect (Bu)2cAMP-induced IL-6 synthesis. In addition, T3 reduced PGF2alpha-induced IL-6 synthesis dose dependently in the range between 10 pM and 10 nM. T3 also inhibited IL-6 synthesis induced by 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C. On the other hand, T3 markedly enhanced IL-1-induced IL-6 synthesis. This enhancement by T3 was potentiated in protein kinase C down-regulated cells. T3 hardly affected the protein kinase C activation induced by PGF2alpha or IL-1. These results strongly suggest that T3 modulates IL-6 synthesis at two points in osteoblasts as follows; one is exerted at the point between adenylate cyclase and protein kinase A, and the other is at a point downstream from protein kinase C activation.
authors.affiliation: Department of Internal Medicine, Chubu National Hospital, National Institute for Longevity Sciences, Obu, Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tokuda
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
authors.forename: A
authors.initials: A
authors.lastname: Harada
authors.forename: K I
authors.initials: KI
authors.lastname: Isobe
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D015237:Dinoprost / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014284:Triiodothyronine; D005576:Colforsin; D003994:Bucladesine; D015237:Dinoprost; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate