Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.176
4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice
Ju-Hyun Lee and Dong-Soon Im*
Laboratory of Pharmacology, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
*E-mail: imds@khu.ac.kr
Tel: +82-2-961-9377, Fax: +82-2-961-9580
Received: October 8, 2020; Revised: March 22, 2021; Accepted: March 23, 2021; Published online: April 20, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, in vivo efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.
Keywords: FFA2, Free fatty acid receptor 2, Short-chain fatty acids, Anti-allergic, Anti-asthmatic, Degranulation


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