Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis

Suoyi Feng,1,2 Longzhu Ju,1 Ziqi Shao,1,3 Mark Grzanna,2 Lu Jia,4 Ming Liu5 1College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province 150030, People’s Republic of China; 2Science Department, The John Carroll School, Bel Air, Maryland, USA; 3College o...

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Autores principales:	Feng S, Ju L, Shao Z, Grzanna M, Jia L, Liu M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	allergic rhinitis inflammation c-c chemokine receptor type 1 antagonist cytokines chemokines Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/905ec8bc5e74422f9e755e3ded08c71b
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spelling	oai:doaj.org-article:905ec8bc5e74422f9e755e3ded08c71b2021-12-02T10:43:35ZTherapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis1178-7031https://doaj.org/article/905ec8bc5e74422f9e755e3ded08c71b2020-07-01T00:00:00Zhttps://www.dovepress.com/therapeutic-effect-of-c-c-chemokine-receptor-type-1-ccr1-antagonist-bx-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Suoyi Feng,1,2 Longzhu Ju,1 Ziqi Shao,1,3 Mark Grzanna,2 Lu Jia,4 Ming Liu5 1College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province 150030, People’s Republic of China; 2Science Department, The John Carroll School, Bel Air, Maryland, USA; 3College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province 430070, People’s Republic of China; 4School of Basic Medical Science, Shanxi University of Traditional Chinese Medicine, Jinzhong, Shanxi Province 030619, People’s Republic of China; 5State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang Province 150069, People’s Republic of ChinaCorrespondence: Suoyi FengScience Department, The John Carroll School, 703 E Churchville Road, Bel Air, Maryland 21014, USAEmail fengsuoyi2001@hotmail.comMing LiuState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, 678 Haping Road, Harbin, Heilongjiang Province 150069, People’s Republic of ChinaEmail liuming04@126.comObjective and Design: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory respiratory hypersensitivity characterized by elevated Th2 cytokines and infiltration of inflammatory cells to nasal tissues. BX471 is a small-molecule C-C chemokine receptor type 1 (CCR1) antagonist involved in suppression of inflammation via blocking of primary ligands. In this study, we examined the anti-inflammatory effect of BX471 on ovalbumin (OVA)-induced AR mice model.Materials and Methods: Levels of OVA-specific IgE and Th1 cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Nasal expression of proinflammatory mediators was assessed by real-time polymerase chain reaction (RT-qPCR). Nasal-cavity sections were stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to study eosinophil infiltration and goblet cell metaplasia. Relative protein levels of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-like Receptor 4 (TLR4) and Toll-like-receptor 2 (TLR2) were assessed by Western Blot. Percentage of CD4+CD25+Foxp3+ T regulatory cells (Treg) was measured by flow cytometry.Results: Mice treated with BX471 showed significantly relieved sneezing and nasal-rubbing behaviors. The expression of nasal proinflammatory factors was significantly downregulated by BX471, and protein levels of tumor necrosis factor alpha (TNF- α) and NF-kB were suppressed. Blockade of CCR1 ligands inhibited eosinophil recruitment in nasal cavity. In addition, Treg cells population were upregulated in BX471-treated mice.Conclusion: BX471 exerts anti-inflammatory effects in a mouse model of AR by inhibiting CCR1-mediated TNF-α production, which subsequently suppresses NF-kB activation in inflammatory cells, leading to a decrease in Th2 cytokines, IL-1β, VCAM-1, GM-CSF, RANTES, and MIP-1α expression levels, thus inhibiting eosinophil recruitment to nasal mucosa. In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population. Overall, BX471 represents a promising therapeutic strategy against AR.Keywords: allergic rhinitis (AR), inflammation, C-C chemokine receptor type 1 antagonist, cytokines, chemokinesFeng SJu LShao ZGrzanna MJia LLiu MDove Medical Pressarticleallergic rhinitisinflammationc-c chemokine receptor type 1 antagonistcytokineschemokinesPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 343-356 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	allergic rhinitis inflammation c-c chemokine receptor type 1 antagonist cytokines chemokines Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	allergic rhinitis inflammation c-c chemokine receptor type 1 antagonist cytokines chemokines Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Feng S Ju L Shao Z Grzanna M Jia L Liu M Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
description	Suoyi Feng,1,2 Longzhu Ju,1 Ziqi Shao,1,3 Mark Grzanna,2 Lu Jia,4 Ming Liu5 1College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province 150030, People’s Republic of China; 2Science Department, The John Carroll School, Bel Air, Maryland, USA; 3College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province 430070, People’s Republic of China; 4School of Basic Medical Science, Shanxi University of Traditional Chinese Medicine, Jinzhong, Shanxi Province 030619, People’s Republic of China; 5State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang Province 150069, People’s Republic of ChinaCorrespondence: Suoyi FengScience Department, The John Carroll School, 703 E Churchville Road, Bel Air, Maryland 21014, USAEmail fengsuoyi2001@hotmail.comMing LiuState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, 678 Haping Road, Harbin, Heilongjiang Province 150069, People’s Republic of ChinaEmail liuming04@126.comObjective and Design: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory respiratory hypersensitivity characterized by elevated Th2 cytokines and infiltration of inflammatory cells to nasal tissues. BX471 is a small-molecule C-C chemokine receptor type 1 (CCR1) antagonist involved in suppression of inflammation via blocking of primary ligands. In this study, we examined the anti-inflammatory effect of BX471 on ovalbumin (OVA)-induced AR mice model.Materials and Methods: Levels of OVA-specific IgE and Th1 cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Nasal expression of proinflammatory mediators was assessed by real-time polymerase chain reaction (RT-qPCR). Nasal-cavity sections were stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to study eosinophil infiltration and goblet cell metaplasia. Relative protein levels of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-like Receptor 4 (TLR4) and Toll-like-receptor 2 (TLR2) were assessed by Western Blot. Percentage of CD4+CD25+Foxp3+ T regulatory cells (Treg) was measured by flow cytometry.Results: Mice treated with BX471 showed significantly relieved sneezing and nasal-rubbing behaviors. The expression of nasal proinflammatory factors was significantly downregulated by BX471, and protein levels of tumor necrosis factor alpha (TNF- α) and NF-kB were suppressed. Blockade of CCR1 ligands inhibited eosinophil recruitment in nasal cavity. In addition, Treg cells population were upregulated in BX471-treated mice.Conclusion: BX471 exerts anti-inflammatory effects in a mouse model of AR by inhibiting CCR1-mediated TNF-α production, which subsequently suppresses NF-kB activation in inflammatory cells, leading to a decrease in Th2 cytokines, IL-1β, VCAM-1, GM-CSF, RANTES, and MIP-1α expression levels, thus inhibiting eosinophil recruitment to nasal mucosa. In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population. Overall, BX471 represents a promising therapeutic strategy against AR.Keywords: allergic rhinitis (AR), inflammation, C-C chemokine receptor type 1 antagonist, cytokines, chemokines
format	article
author	Feng S Ju L Shao Z Grzanna M Jia L Liu M
author_facet	Feng S Ju L Shao Z Grzanna M Jia L Liu M
author_sort	Feng S
title	Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
title_short	Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
title_full	Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
title_fullStr	Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
title_full_unstemmed	Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis
title_sort	therapeutic effect of c-c chemokine receptor type 1 (ccr1) antagonist bx471 on allergic rhinitis
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/905ec8bc5e74422f9e755e3ded08c71b
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Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis

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