title: Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1.
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.
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors: Tiina
authors: T
authors: Keränen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors: Tuija
authors: T
authors: Hömmö
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors: Mari
authors: M
authors: Hämäläinen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors: Eeva
authors: E
authors: Moilanen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
authors: Riku
authors: R
authors: Korhonen
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013726:Terbutaline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D054638:Dual Specificity Phosphatase 1; D013726:Terbutaline; D000420:Albuterol