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

Rees, Dafydd Aled ORCID: https://orcid.org/0000-0002-1165-9092, 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:	17 Oct 2022 08:33
URI:	https://orca.cardiff.ac.uk/id/eprint/431

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