Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Son, So-Eun, Koh, Jung-Min, Im, Dong-Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100770/
https://www.ncbi.nlm.nih.gov/pubmed/35563671
http://dx.doi.org/10.3390/ijms23095270
_version_ 1784706928099721216
author Son, So-Eun
Koh, Jung-Min
Im, Dong-Soon
author_facet Son, So-Eun
Koh, Jung-Min
Im, Dong-Soon
author_sort Son, So-Eun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9100770
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91007702022-05-14 Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice Son, So-Eun Koh, Jung-Min Im, Dong-Soon Int J Mol Sci Article 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. MDPI 2022-05-09 /pmc/articles/PMC9100770/ /pubmed/35563671 http://dx.doi.org/10.3390/ijms23095270 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Son, So-Eun
Koh, Jung-Min
Im, Dong-Soon
Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title_full Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title_fullStr Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title_full_unstemmed Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title_short Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice
title_sort activation of free fatty acid receptor 4 (ffa4) ameliorates ovalbumin-induced allergic asthma by suppressing activation of dendritic and mast cells in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100770/
https://www.ncbi.nlm.nih.gov/pubmed/35563671
http://dx.doi.org/10.3390/ijms23095270
work_keys_str_mv AT sonsoeun activationoffreefattyacidreceptor4ffa4amelioratesovalbumininducedallergicasthmabysuppressingactivationofdendriticandmastcellsinmice
AT kohjungmin activationoffreefattyacidreceptor4ffa4amelioratesovalbumininducedallergicasthmabysuppressingactivationofdendriticandmastcellsinmice
AT imdongsoon activationoffreefattyacidreceptor4ffa4amelioratesovalbumininducedallergicasthmabysuppressingactivationofdendriticandmastcellsinmice