Oleoylethanolamide induces eosinophilic airway inflammation in bronchial asthma

Eun-Kyung Kwon,Ga-Young Ban,Hee-Ra Lee,Soyoon Sim,Hae-Sim Park,Hyoung Su Kim,Young-Min Ye,Il-Hee Yoon,Youngwoo Choi,Ha-Kyeong Won,Yoo Seob Shin

doi:10.1038/s12276-021-00622-x

Abstract

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils.

Highlights

Asthma is a common chronic respiratory disease that affects 1–18% of the population worldwide[1]
The increased mRNA expression of these cytokines was not observed in the LTE4-alone group, the administration of OEA after pretreatment with LTE4 showed a synergistic effect on inflammation in A549 cells
OEA increased the numbers of type 2 (T2) cytokinereleasing ILC2s in mice, and these results were consistent with the activation of peripheral eosinophils in asthmatic patients

Summary

Introduction

Asthma is a common chronic respiratory disease that affects 1–18% of the population worldwide[1]. The prevalence of asthma has steadily increased over the past decade from 1.6 to 2.2% in Korea. A previous study reported that high levels of blood OEA correlated with a decline in forced expiratory volume in 1 s (FEV1) in patients with cystic fibrosis[9]. In a recent study of severe asthmatic patients, the levels of serum OEA increased with increasing asthma severity[10]. We have reported significantly increased levels of OEA in patients with aspirin-exacerbated respiratory disease (AERD)[11]. The increased levels of OEA in asthma can be defensive or a pathological mechanism. Unlike those of other endocannabinoids, the mechanism of OEA in airway inflammation remains to be elucidated

Methods

Results

Conclusion