LAUSR

HighlightsIn general, ligand‐&bgr;2‐receptor engagement activates ERK pathway.In this study, &bgr;2‐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 &bgr;2‐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. &bgr;2‐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 &bgr;2‐receptor agonists salbutamol and terbutaline on the production of inflammatory factors in macrophages. We found that &bgr;2‐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 &bgr;2‐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 &bgr;2‐receptor agonists may contribute to the clinical effects of these drugs.