Inhibition of NF-kappa B-mediated gene transcription by the human A(2B) adenosine receptor in Chinese hamster ovary cells

NF-kappaB is a transcription factor that plays a vital role in regulating i nducible gene expression in immune and inflammatory responses. In view of t he well documented effects of adenosine on immune and inflammatory response s, we have explored whether adenosine A(1), A(2B) and A(3) receptors regula te NF-kappaB activity in transfected Chinese hamster ovary (CHO) cells usin g a luciferase reporter gene construct. No increases in NF-kappaB activity were observed in CHO-A(1), -A(2B) and -A(3) cells stimulated with the non-s elective adenosine receptor agonist 5 ' -N-ethyl-carboxamidoadenosine. Elev ating intracellular cyclic AMP (cAMP) levels using forskolin (direct activa tor of adenylyl cyclase) and rolipram (type IV, cAMP-specific phosphodieste rase inhibitor), inhibited NF-kappaB activity in CHO cells. Adenosine A(2B) receptor stimulation also inhibited NF-kappaB activity, whereas adenosine A(1) and A(3) receptor activation had no effect. These data reflect the kno wn coupling of adenosine A(2B) receptors to increases in cAMP. In conclusio n, adenosine A(1), A(2B) and A(3) receptors do not directly activate NF-kap paB in CHO cells. However, adenosine A(2B) receptor activation significantl y inhibited NF-kappaB activity. Inhibition of NF-kappaB activity by the ade nosine A(2B) receptor may contribute to the anti-inflammatory effects of ad enosine.