beta(2)-receptor agonists salbutamol and terbutaline attenuated cytokine production by suppressing ERK pathway through cAMP in macrophages

摘要

beta(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. beta(2)-receptor activation is considered to lead to the activation of ERIC pathway through G-protein- and cAMP-independent mechanisms. In this study, we investigated the effects of beta(2)-receptor agonists salbutamol and terbutaline on the production of inflammatory factors in macrophages. We found that beta(2)-receptor agonists inhibited LPS-induced ERIC phosphorylation and the production of MCP-1. A chemical CAMP analog 8-Br-cAMP also inhibited ERIC phosphorylation and TNF and MCP-1 release. As expected, MAPK/ERK kinase (MEK)1/2 inhibitor PD 0325901 inhibited ERIC phosphorylation and suppressed both TNF and MCP-1 production. In conclusion, we suggest that beta(2)-receptor agonists salbutamol and terbutaline inhibit inflammatory gene expression partly by a mechanism dependent on cAMP leading to the inhibition of ERIC signaling in macrophages. Observed anti-inflammatory effects of beta(2)-receptor agonists may contribute to the clinical effects of these drugs. (C) 2016 Elsevier Ltd. All rights reserved.