title: Inhibition of NF-kappaB-mediated gene transcription by the human A2B adenosine receptor in Chinese hamster ovary cells.
abstract: NF-kappaB is a transcription factor that plays a vital role in regulating inducible gene expression in immune and inflammatory responses. In view of the well documented effects of adenosine on immune and inflammatory responses, we have explored whether adenosine A1, A2B and A3 receptors regulate NF-kappaB activity in transfected Chinese hamster ovary (CHO) cells using a luciferase reporter gene construct. No increases in NF-kappaB activity were observed in CHO-A1, -A2B and -A3 cells stimulated with the non-selective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine. Elevating intracellular cyclic AMP (cAMP) levels using forskolin (direct activator of adenylyl cyclase) and rolipram (type IV, cAMP-specific phosphodiesterase inhibitor), inhibited NF-kappaB activity in CHO cells. Adenosine A2B receptor stimulation also inhibited NF-kappaB activity, whereas adenosine A1 and A3 receptor activation had no effect. These data reflect the known coupling of adenosine A2B receptors to increases in cAMP. In conclusion, adenosine A1, A2B and A3 receptors do not directly activate NF-kappaB in CHO cells. However, adenosine A2B receptor activation significantly inhibited NF-kappaB activity. Inhibition of NF-kappaB activity by the adenosine A2B receptor may contribute to the anti-inflammatory effects of adenosine.
authors.affiliation: Department of Life Sciences, Nottingham Trent University, UK.
authors.forename: P
authors.initials: P
authors.lastname: Combes
authors.forename: J M
authors.initials: JM
authors.lastname: Dickenson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D006224:Cricetinae; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1