Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK
| Autor: | D Aled, Rees, B Mary, Lewis, Mark D, Lewis, Karen, Francis, Maurice F, Scanlon, Jack, Ham |
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| Rok vydání: | 2003 |
| Předmět: |
Adenosine
Indoles Interleukin-6 Vascular Endothelial Growth Factors Adenosine-5'-(N-ethylcarboxamide) Receptor Adenosine A2B p38 Mitogen-Activated Protein Kinases Dexamethasone Pyrrolidinones Adenosine A2 Receptor Antagonists Androstadienes Mice Phosphatidylinositol 3-Kinases Pituitary Gland Anterior Type C Phospholipases Papers Animals Pyrroles Estrenes Mitogen-Activated Protein Kinases Wortmannin Cells Cultured Protein Kinase C Phosphoinositide-3 Kinase Inhibitors |
| Zdroj: | British journal of pharmacology. 140(4) |
| ISSN: | 0007-1188 |
| Popis: | Activation of adenosine receptors in folliculostellate (FS) cells of the pituitary gland leads to the secretion of IL-6 and vascular endothelial growth factor (VEGF). We investigated the action of adenosine A2 receptor agonists on IL-6 and VEGF secretion in two murine FS cell lines (TtT/GF and Tpit/F1), and demonstrated a rank order of potency, 5'-N-ethylcarboxamidoadenosine (NECA)2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosineadenosine, suggesting mediation via the A2b receptor. NECA-mediated IL-6 release was inhibited by the PLC inhibitor 1-[6-((17beta-3-methoxyestra-1,3,5(10)-tiene-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione, the PI3 kinase inhibitor wortmannin and the PKC inhibitors bisindolylmaleimide 1 and bisindolymaleimide X1 HCl (Ro-32-0432). NECA-mediated IL-6 release was attenuated (50%) by the extracellular signal-regulated kinase MAPK inhibitor 2'-amino-3'-methoxyflavone, and completely (95%) inhibited by the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole. NECA stimulates p38 MAPK phosphorylation that is inhibited by Ro-32-0432 but not by wortmannin. Dexamethasone inhibits NECA-stimulated IL-6 and VEGF secretion. These findings indicate that adenosine can stimulate IL-6 secretion in FS cells via the A2b receptor coupled principally to PLC/PKC and p38 MAPK; such an action may be important in the modulation of inflammatory response processes in the pituitary gland. |
| Databáze: | OpenAIRE |
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