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

Tiina Keränen; Tuija Hömmö; Mari Hämäläinen; Eeva Moilanen; Riku Korhonen

doi:10.1371/journal.pone.0148144

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

PLoS One. 2016 Feb 5;11(2):e0148144. doi: 10.1371/journal.pone.0148144. eCollection 2016.

Authors

Tiina Keränen¹, Tuija Hömmö¹, Mari Hämäläinen¹, Eeva Moilanen¹, Riku Korhonen¹

Affiliation

¹ The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic beta-2 Receptor Agonists / pharmacology*
Albuterol / pharmacology*
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line
Dual Specificity Phosphatase 1 / genetics
Dual Specificity Phosphatase 1 / metabolism*
Gene Expression Regulation, Enzymologic / drug effects
Macrophages / drug effects
Macrophages / metabolism
Mice
Mice, Inbred C57BL
Terbutaline / pharmacology*
Tumor Necrosis Factor-alpha / biosynthesis

Substances

Adrenergic beta-2 Receptor Agonists
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Dual Specificity Phosphatase 1
Terbutaline
Albuterol

Grants and funding

This work was financially supported by grants from The Academy of Finland, from the Competitive Research Funding of the Pirkanmaa Hospital District, Finland, and from Tampere Tuberculosis Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.