Β2-receptor agonists salbutamol and terbutaline attenuated cytokine production by suppressing ERK pathway through cAMP in macrophages. (June 2017)

• Record Type: Journal Article
• Authors: Keränen, Tiina; Hömmö, Tuija; Moilanen, Eeva; Korhonen, Riku
• Is Part Of: Cytokine. Volume 94(2017)
• Page Start: 1
• Page End: 7
• Publication Date: 2017-06
• Subjects: COPD chronic obstructive pulmonary disease -- ERK extracellular-regulated kinase -- GPCR G-protein-coupled receptor -- GRK G-protein-coupled receptor kinase -- IL interleukin -- LPS lipopolysaccharide -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemoattractant protein-1 -- MEK1/2 MAPK/ERK kinase -- MKP mitogen-activated protein kinase phosphatase -- PDE phosphodiesterase -- TNF tumor necrosis factor; ERK -- TNF -- MCP-1 -- Salbutamol -- Macrophage -- β2-adrenergic receptor; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.07.016
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: In general, ligand-β2 -receptor engagement activates ERK pathway. In this study, β2 -agonists inhibited TNF and MCP-1 production in macrophages. Inhibition of TNF and MCP-1 production was associated with attenuated ERK signaling. Suppression of ERK pathway was dependent on cAMP signaling. Abstract: β2 -receptor agonists are used in the treatment of inflammatory obstructive lung diseases asthma and COPD as a symptomatic remedy, but they have been suggested to possess anti-inflammatory properties, also. β2 -receptor activation is considered to lead to the activation of ERK pathway through G-protein- and cAMP-independent mechanisms. In this study, we investigated the effects of β2 -receptor agonists salbutamol and terbutaline on the production of inflammatory factors in macrophages. We found that β2 -receptor agonists inhibited LPS-induced ERK phosphorylation and the production of MCP-1. A chemical cAMP analog 8-Br-cAMP also inhibited ERK phosphorylation and TNF and MCP-1 release. As expected, MAPK/ERK kinase (MEK)1/2 inhibitor PD 0325901 inhibited ERK phosphorylation and suppressed both TNF and MCP-1 production. In conclusion, we suggest that β2 -receptor agonists salbutamol and terbutaline inhibit inflammatory gene expression partly by a mechanism dependent on cAMP leading to the inhibition of ERK signaling in macrophages. Observed anti-inflammatory effects of β2 -receptor agonists may contribute to the clinical effects of these drugs.