Abstract
BackgroundDefective absorption of acute allergic airway inflammation is involved in the initiation and development of chronic asthma. After allergen exposure, there is a rapid recruitment of macrophages around the airways, which promote acute inflammatory responses. The Ang-(1−7)/Mas receptor axis reportedly plays protective roles in various tissue inflammation and remodeling processes in vivo. However, the exact role of Mas receptor and their underlying mechanisms during the pathology of acute allergic airway inflammation remains unclear. ObjectiveWe investigated the role of Mas receptor in acute allergic asthma and explored its underlying mechanisms in vitro, aiming to find critical molecules and signal pathways. MethodsMas receptor expression was assessed in ovalbumin (OVA)-induced acute asthmatic murine model. Then we estimated the anti-inflammatory role of Mas receptor in vivo and explored expressions of several known inflammatory cytokines as well as phosphorylation levels of MAPK pathways. Mas receptor functions and underlying mechanisms were studied further in the human bronchial epithelial cell line (16HBE). ResultsMas receptor expression decreased in acute allergic airway inflammation. Multiplex immunofluorescence co-localized Mas receptor and EpCAM, indicated that Mas receptor may function in the bronchial epithelium. Activating Mas receptor through AVE0991 significantly alleviated macrophage infiltration in airway inflammation, accompanied with down-regulation of CCL2 and phosphorylation levels of MAPK pathways. Further studies in 16HBE showed that AVE0991 pre-treatment inhibited LPS-induced or anisomycin-induced CCL2 increase and THP-1 macrophages migration via JNK pathways. ConclusionOur findings suggested that Mas receptor activation significantly attenuated CCL2 dependent macrophage recruitments in acute allergic airway inflammation through JNK pathways, which indicated that Mas receptor, CCL2 and phospho-JNK could be potential targets against allergic airway inflammation.
Highlights
Defective absorption of acute allergic airway inflammation is involved in the initiation and development of chronic asthma
Our findings suggested that Mas receptor activation significantly attenuated C-C Motif Chemokine Ligand 2 (CCL2) dependent macrophage recruitments in acute allergic airway inflammation through c-Jun N-terminal kinase ERK (JNK) pathways, which indicated that Mas receptor, CCL2 and phospho-JNK could be potential targets against allergic airway inflammation
Based on the evidence that chronic OVA challenges reduced the area stained for Mas receptor by 40% [17], we wondered whether decreased expression of Mas receptor existed in acute allergic airway inflammation as well
Summary
Defective absorption of acute allergic airway inflammation is involved in the initiation and development of chronic asthma. There is a rapid recruitment of macrophages around the airways, which promote acute inflammatory responses. The Ang-(1-7)/Mas receptor axis reportedly plays protective roles in various tissue inflammation and remodeling processes in vivo. The exact role of Mas receptor and their underlying mechanisms during the pathology of acute allergic airway inflammation remains unclear. The most effective treatment for asthma is inhaled corticosteroids, with or without long-acting β2-agonist and muscarinic antagonists. Even with appropriate inhaled therapy, a significant number of patients’ asthma is still poorly controlled. The inability to resolve ongoing inflammation may be crucial for the initiation and development of chronic asthma
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