Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1

Mitogen-activated protein kinase phosphatase 1 (MKP-1) expression is induced by inflammatory factors, and it is an endogenous suppressor of inflammatory response. MKP-1 expression is increased by PDE4 inhibitor rolipram suggesting that it is regulated by cAMP-enhancing compounds. Therefore, we investigated the effect of beta(2)-receptor agonists on MKP-1 expression and inflammatory response. We found that beta(2)-receptor agonists salbutamol and terbutaline, as well as 8-Br-cAMP, increased MKP-1 expression. Salbutamol and terbutaline also inhibited p38 MAPK phosphorylation and TNF production in J774 mouse macrophages. Interestingly, salbutamol suppressed carrageenan-induced paw inflammation in wild-type mice, but the effect was attenuated in MKP-1(-/-) mice. In conclusion, these data show that beta(2)-receptor agonists increase MKP-1 expression, which seems to mediate, at least partly, the observed anti-inflammatory effects of beta(2)-receptor agonists.