Premium
Adenosine‐induced IL‐6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK
Author(s) -
Rees D Aled,
Lewis B Mary,
Lewis Mark D,
Francis Karen,
Scanlon Maurice F,
Ham Jack
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705488
Subject(s) - wortmannin , adenosine , medicine , endocrinology , protein kinase c , adenosine receptor , bisindolylmaleimide , mapk/erk pathway , biology , chemistry , receptor , microbiology and biotechnology , kinase , signal transduction , pi3k/akt/mtor pathway , agonist
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 β ‐3‐methoxyestra‐1,3,5(10)‐tiene‐17‐yl)amino)hexyl]‐1 H ‐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)1 H ‐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.British Journal of Pharmacology (2003) 140 , 764–772. doi: 10.1038/sj.bjp.0705488