Cannabinoid receptor 2 as a regulator of inflammation induced oleoylethanolamide in eosinophilic asthma

Abstract

Background: Oleoylethanolamide (OEA), an endogenously generated cannabinoid-like compound, has been reported to be increased in patients with severe asthma and aspirin-exacerbated respiratory disease. Recruitment of activated eosinophils in the airways is a hallmark of bronchial asthma. Objective: We explored the direct contribution of cannabinoid receptor 2 (CB2), a cognate receptor of OEA, which induces eosinophil activation in vitro and in vivo. Methods: We investigated OEA signaling in the eosinophilic cell line dEol-1 in peripheral blood eosinophils from people with asthma. In order to confirm whether eosinophil activation by OEA is CB2 dependent or not, CB2 small interfering RNA and the CB2 antagonist SR144528 were used. The numbers of airway inflammatory cells and the levels of cytokines were measured in bronchoalveolar lavage fluid, and airway hyperresponsiveness was examined in the BALB/c mice. Results: CB2 expression was increased after OEA treatment in both peripheral blood eosinophils and dEol-1 cells. It was also elevated after OEA-induced recruitment of eosinophils to the lungs in vivo. However, SR144528 treatment reduced the activation of peripheral blood eosinophils from asthmatic patients. Furthermore, CB2 knockdown decreased the activation of dEol-1 cells and the levels of inflammatory and type 2 cytokines. SR144528 treatment alleviated airway hyperresponsiveness and eosinophil recruitment to the lungs in vivo. Conclusion: CB2 may contribute to the pathogenesis of eosinophilic asthma. Our results provide new insight into the molecular mechanism of signal transduction by OEA in eosinophilic asthma.