Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1 |
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| Authors: | Tiina Ker?nen Tuija H?mm? Mari H?m?l?inen Eeva Moilanen Riku Korhonen |
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| Institution: | The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland;French National Centre for Scientific Research, FRANCE |
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| Abstract: | 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 β2-receptor agonists on MKP-1 expression and inflammatory response. We found that β2-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 β2-receptor agonists increase MKP-1 expression, which seems to mediate, at least partly, the observed anti-inflammatory effects of β2-receptor agonists. |
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