[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4062/biomolther.2020.176

4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice

Lee, Ju-Hyun (Laboratory of Pharmacology, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)
Im, Dong-Soon (Laboratory of Pharmacology, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)

Publication Information

Biomolecules & Therapeutics / v.29, no.4, 2021 , pp. 427-433 More about this Journal

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;

Citations & Related Records

Times Cited By KSCI : 1 (Citation Analysis)

Reference
Cited By KSCI

1	Kim, M. J. and Im, D. S. (2019) Suppressive effects of type I angiotensin receptor antagonists, candesartan and irbesartan on allergic asthma. Eur. J. Pharmacol. 852, 25-33. DOI
2	Im, D. S. (2004) Discovery of new G protein-coupled receptors for lipid mediators. J. Lipid Res. 45, 410-418. DOI
3	Melhem, H., Kaya, B., Ayata, C. K., Hruz, P. and Niess, J. H. (2019) Metabolite-sensing G protein-coupled receptors connect the dietmicrobiota-metabolites axis to inflammatory bowel disease. Cells 8, 450. DOI
4	Barnes, P. J. (2013) Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 131, 636-645. DOI
5	Boucherat, O., Boczkowski, J., Jeannotte, L. and Delacourt, C. (2013) Cellular and molecular mechanisms of goblet cell metaplasia in the respiratory airways. Exp. Lung Res. 39, 207-216. DOI
6	Huang, J., Su, M., Lee, B., Kim, M., Jung, J. H. and Im, D. (2018) Suppressive effect of 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione on ovalbumin-induced allergic asthma. Biomol. Ther. (Seoul) 26, 539-545. DOI
7	Colucci, R., Fornai, M., Tuccori, M., Antonioli, L., Pasqualetti, G., Blandizzi, C. and Tacca, M. D. (2007) Tolerability profiles of leukotriene receptor antagonists and long-acting β2-adrenoceptor agonists in combination with inhaled corticosteroids for treatment of asthma: a review. J. Asthma 44, 411-422. DOI
8	He, Y., Wen, Q., Yao, F., Xu, D., Huang, Y. and Wang, J. (2017) Gutlung axis: the microbial contributions and clinical implications. Crit. Rev. Microbiol. 43, 81-95. DOI
9	Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., Sugimoto, Y., Miyazaki, S. and Tsujimoto, G. (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 11, 90-94. DOI
10	Itoh, Y., Kawamata, Y., Harada, M., Kobayashi, M., Fujii, R., Fukusumi, S., Ogi, K., Hosoya, M., Tanaka, Y., Uejima, H., Tanaka, H., Maruyama, M., Satoh, R., Okubo, S., Kizawa, H., Komatsu, H., Matsumura, F., Noguchi, Y., Shinohara, T., Hinuma, S., Fujisawa, Y. and Fujino, M. (2003) Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature 422, 173-176. DOI
11	Smith, N. J., Ward, R. J., Stoddart, L. A., Hudson, B. D., Kostenis, E., Ulven, T., Morris, J. C., Trankle, C., Tikhonova, I. G., Adams, D. R. and Milligan, G. (2011) Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator. Mol. Pharmacol. 80, 163-173. DOI
12	Le Poul, E., Loison, C., Struyf, S., Springael, J., Lannoy, V., Decobecq, M., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., Parmentier, M. and Detheux, M. (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481-25489. DOI
13	Jin, Y. Y., Shi, Z. Q., Chang, W. Q., Guo, L. X., Zhou, J. L., Liu, J. Q., Liu, L. F. and Xin, G. Z. (2018) A chemical derivatization based UHPLC-LTQ-Orbitrap mass spectrometry method for accurate quantification of short-chain fatty acids in bronchoalveolar lavage fluid of asthma mice. J. Pharm. Biomed. Anal. 161, 336-343. DOI
14	Lee-Sarwar, K. A., Kelly, R. S., Lasky-Su, J., Zeiger, R. S., O'Connor, G. T., Sandel, M. T., Bacharier, L. B., Beigelman, A., Rifas-Shiman, S. L., Carey, V. J., Harshfield, B. J., Laranjo, N., Gold, D. R., Weiss, S. T. and Litonjua, A. A. (2020) Fecal short-chain fatty acids in pregnancy and offspring asthma and allergic outcomes. J. Allergy Clin. Immunol. Pract. 8, 1100-1102.e13. DOI
15	Romagnani, S. (2002) Cytokines and chemoattractants in allergic inflammation. Mol. Immunol. 38, 881-885. DOI
16	Macia, L., Tan, J., Vieira, A. T., Leach, K., Stanley, D., Luong, S., Maruya, M., McKenzie, C. I., Hijikata, A., Wong, C., Binge, L., Thorburn, A. N., Chevalier, N., Ang, C., Marino, E., Robert, R., Offermanns, S., Teixeira, M. M., Moore, R. J., Flavell, R. A., Fagarasan, S. and Mackay, C. R. (2015) Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734. DOI
17	Miyamoto, J., Kasubuchi, M., Nakajima, A. and Kimura, I. (2016) Anti-inflammatory and insulin-sensitizing effects of free fatty acid receptors. In Free Fatty Acid Receptors, pp. 221-231. Springer.
18	Park, S. J. and Im, D. S. (2019) Deficiency of sphingosine-1-phosphate receptor 2 (S1P2) attenuates bleomycin-induced pulmonary fibrosis. Biomol. Ther. (Seoul) 27, 318-326. DOI
19	Pascual, R. M. and Peters, S. P. (2005) Airway remodeling contributes to the progressive loss of lung function in asthma: an overview. J. Allergy Clin. Immunol. 116, 477-486. DOI
20	Qian, L., Lu, L., Huang, L., Wen, Q., Xie, J., Jin, W., Li, H. and Jiang, L. (2019) The effect of neonatal maternal separation on short-chain fatty acids and airway inflammation in adult asthma mice. Allergol. Immunopathol. 47, 2-11. DOI
21	Sun, M., Wu, W., Liu, Z. and Cong, Y. (2017) Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 52, 1-8. DOI
22	Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M. and Olefsky, J. M. (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687-698. DOI
23	Tan, J. K., McKenzie, C., Marino, E., Macia, L. and Mackay, C. R. (2017) Metabolite-sensing G protein-coupled receptors-facilitators of diet-related immune regulation. Annu. Rev. Immunol. 35, 371-402. DOI
24	Theiler, A., Barnthaler, T., Platzer, W., Richtig, G., Peinhaupt, M., Rittchen, S., Kargl, J., Ulven, T., Marsh, L. M., Marsche, G., Schuligoi, R., Sturm, E. M. and Heinemann, A. (2019) Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. J. Allergy Clin. Immunol. 144, 764-776. DOI
25	Theoharides, T. C. and Kalogeromitros, D. (2006) The critical role of mast cells in allergy and inflammation. Ann. N. Y. Acad. Sci. 1088, 78-99. DOI
26	Lee, T., Schwandner, R., Swaminath, G., Weiszmann, J., Cardozo, M., Greenberg, J., Jaeckel, P., Ge, H., Wang, Y., Jiao, X., Liu, J., Kayser, F., Tian, H. and Li, Y. (2008) Identification and functional characterization of allosteric agonists for the G protein-coupled receptor FFA2. Mol. Pharmacol. 74, 1599-1609. DOI
27	Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., Xavier, R. J., Teixeira, M. M. and Mackay, C. R. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282-1286. DOI
28	Naclerio, R. (1999) Clinical manifestations of the release of histamine and other inflammatory mediators. J. Allergy Clin. Immunol. 103, S382-S385. DOI
29	Thio, C. L., Chi, P., Lai, A. C. and Chang, Y. (2018) Regulation of type 2 innate lymphoid cell-dependent airway hyperreactivity by butyrate. J. Allergy Clin. Immunol. 142, 1867-1883.e12. DOI
30	Ulven, T. (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front. Endocrinol. 3, 111. DOI
31	Tiwari, A. (2010) GPR43: an emerging target for the potential treatment of type 2 diabetes, obesity and insulin resistance. Curr. Opin. Investig. Drugs 11, 385-393.
32	Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L. P., Harris, N. L. and Marsland, B. J. (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159-166. DOI
33	Wardlaw, A., Brightling, C., Green, R., Woltmann, G., Bradding, P. and Pavord, I. (2002) New insights into the relationship between airway inflammation and asthma. Clin. Sci. 103, 201-211. DOI
34	Young, R. P., Hopkins, R. J. and Marsland, B. (2016) The gut-liver-lung axis. Modulation of the innate immune response and its possible role in chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 54, 161-169. DOI
35	Im, D. S. (2013) Intercellular lipid mediators and GPCR drug discovery. Biomol. Ther. (Seoul) 21, 411-422. DOI
36	Aoki, H., Hisada, T., Ishizuka, T., Utsugi, M., Ono, A., Koga, Y., Sunaga, N., Nakakura, T., Okajima, F., Dobashi, K. and Mori, M. (2010) Protective effect of resolvin E1 on the development of asthmatic airway inflammation. Biochem. Biophys. Res. Commun. 400, 128-133. DOI
37	Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., Pike, N. B., Strum, J. C., Steplewski, K. M., Murdock, P. R., Holder, J. C., Marshall, F. H., Szekeres, P. G., Wilson, S., Ignar, D. M., Foord, S. M., Wise, A. and Dowell, S. J. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278, 11312-11319. DOI
38	Heo, J. Y. and Im, D. S. (2019) Anti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experiments. Int. Immunopharmacol. 67, 69-77. DOI