Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice

被引:17
|
作者
Son, So-Eun [1 ]
Koh, Jung-Min [2 ]
Im, Dong-Soon [1 ,3 ]
机构
[1] Kyung Hee Univ, Grad Sch, Dept Biomed & Pharmaceut Sci, Seoul 02447, South Korea
[2] Univ Ulsan, Div Endocrinol & Metab, Asan Med Ctr, Coll Med, Seoul 05505, South Korea
[3] Kyung Hee Univ, Grad Sch, Dept Basic Pharmaceut Sci, Seoul 02447, South Korea
基金
新加坡国家研究基金会;
关键词
allergy; asthma; free fatty acid receptor 4; FFA4; omega-3 polyunsaturated fatty acids; DAMPENS AIRWAY INFLAMMATION; DIETARY SUPPLEMENTATION; INSULIN-RESISTANCE; RESOLVIN E1; GPR120; OMEGA-3-FATTY-ACIDS; RESOLUTION; LIPIDS; MODEL;
D O I
10.3390/ijms23095270
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epidemiological and clinical studies have suggested that intake of n-3 polyunsaturated fatty acids (PUFA) reduces the incidence of allergic airway diseases and improves pulmonary function in patients with allergic asthma. However, the pharmacological targets of PUFA have not been elucidated upon. We investigated whether free fatty acid receptor 4 (FFA4, also known as GPR120) is a molecular target for beneficial PUFA in asthma therapy. In an ovalbumin (OVA)-induced allergic asthma model, compound A (a selective agonist of FFA4) was administrated before OVA sensitization or OVA challenge in FFA4 wild-type (WT) and knock-out (KO) mice. Compound A treatment of RBL-2H3 cells suppressed mast cell degranulation in vitro in a concentration-dependent manner. Administration of compound A suppressed in vivo allergic characteristics in bronchoalveolar lavage fluid (BALF) and lungs, such as inflammatory cytokine levels and eosinophil accumulation in BALF, inflammation and mucin secretion in the lungs. Compound A-induced suppression was not only observed in mice treated with compound A before OVA challenge, but in mice treated before OVA sensitization as well, implying that compound A acts on mast cells as well as dendritic cells. Furthermore, this suppression by compound A was only observed in FFA4-WT mice and was absent in FFA4-KO mice, implying that compound A action is mediated through FFA4. Activation of FFA4 may be a therapeutic target of PUFA in allergic asthma by suppressing the activation of dendritic cells and mast cells, suggesting that highly potent specific agonists of FFA4 could be a novel therapy for allergic asthma.
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页数:15
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