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Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK

Rees, Dafydd Aled, Lewis, Barbara Mary, Lewis, Mark David, Francis, Karen, Scanlon, Maurice Francis and Ham, Jack 2003. Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK. British Journal of Pharmacology 140 (4) , pp. 764-72. 10.1038/sj.bjp.0705488

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Abstract

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-ethylcarboxamidoadenosine>adenosine, suggesting mediation via the A2b receptor. NECA-mediated IL-6 release was inhibited by the PLC inhibitor 1-[6-((17?-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Adenosine; A2b receptor; IL-6; folliculostellate cells; PKC; p38 MAPK; pituitary gland
ISSN: 1476-5381
Last Modified: 18 Oct 2017 08:24
URI: http://orca.cf.ac.uk/id/eprint/431

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