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Article

CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response

  • Authors:
    • Huilong Chen
    • Xiangqin Xu
    • Jieming Teng
    • Sheng Cheng
    • Hansvin Bunjhoo
    • Yong Cao
    • Jin Liu
    • Jungang Xie
    • Congyi Wang
    • Yongjian Xu
    • Weining Xiong
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Center for Biomedical Research, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
  • Pages: 1865-1870
    |
    Published online on: March 10, 2016
       https://doi.org/10.3892/etm.2016.3141
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Abstract

Accumulating evidence suggests that chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) may contribute to the pathogenesis of allergic asthma. However, the underlying molecular mechanisms remain to be fully understood. T-helper 17 cells (Th17) and T-cytotoxic 17 cells (Tc17) have been implicated in the development of several allergic disorders, including asthma. The present study aimed to explore the association between CXCL12 signaling and Th17/Tc17 cells in the development of asthma. Ovalbumin (OVA)-sensitized BALB/c mice were treated with AMD3100, a specific CXCR4 antagonist, prior to OVA challenge. Following the final allergen (OVA) challenge, airway responsiveness to methacholine, influx of inflammatory cells to the airway, and cytokine levels in the bronchoalveolar lavage fluids (BALF) and lung homogenate were assessed. Interleukin (IL)‑17‑expressing CD3+CD8‑ lymphocytes (Th17 cells) and IL‑17+CD3+CD8+ lymphocytes (Tc17 cells) isolated from lung tissue samples were detected by flow cytometry. The results of the present study demonstrated that administration of AMD3100 significantly decreased airway responsiveness to methacholine, attenuated the influx of inflammatory cells to the airway and reduced the levels of IL‑4, IL‑5 and IL‑13 in the BALF. Furthermore, AMD3100 significantly reduced the increased number of lung Th17 and Tc17 cells as well as the levels of IL‑17 in the lung homogenate induced by OVA challenge. In conclusion, the CXCR4 inhibitor suppresses the asthmatic response, which is associated with attenuation of the Th17 and Tc17 cell immune response.
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1 

Wills-Karp M, Nathan A, Page K and Karp CL: New insights into innate immune mechanisms underlying allergenicity. Mucosal Immunol. 3:104–110. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Shirozu M, Nakano T, Inazawa J, Tashiro K, Tada H, Shinohara T and Honjo T: Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics. 28:495–500. 1995. View Article : Google Scholar : PubMed/NCBI

3 

McQuibban GA, Butler GS, Gong JH, Bendall L, Power C, Clark-Lewis I and Overall CM: Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem. 276:43503–43508. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Daubeuf F, Hachet-Haas M, Gizzi P, Gasparik V, Bonnet D, Utard V, Hibert M, Frossard N and Galzi JL: An antedrug of the CXCL12 neutraligand blocks experimental allergic asthma without systemic effect in mice. J Biol Chem. 288:11865–11876. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Lukacs NW, Berlin A, Schols D, Skerlj RT and Bridger GJ: AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway hyperreactivity. Am J Pathol. 160:1353–1360. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Gonzalo JA, Lloyd CM, Peled A, Delaney T, Coyle AJ and Gutierrez-Ramos JC: Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease. J Immunol. 165:499–508. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Negrete-Garcia MC, Velazquez JR, Popoca-Coyotl A, Montes-Vizuet AR, Juárez-Carvajal E and Teran LM: Chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 is associated with leukocyte recruitment in asthma. Chest. 138:100–106. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J and Chakir J: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 108:430–438. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP and Hamid Q: Airway remodeling-associated mediators in moderate to severe asthma: Effect of steroids on TGF-beta, IL-11, IL-17 and type I and type III collagen expression. J Allergy Clin Immunol. 111:1293–1298. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M and Iwakura Y: Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity. 17:375–387. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Barczyk A, Pierzchala W and Sozanska E: Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 97:726–733. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, Fossiez F, Ryffel B and Schnyder B: Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med. 203:2715–2725. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Wakashin H, Hirose K, Maezawa Y, Kagami S, Suto A, Watanabe N, Saito Y, Hatano M, Tokuhisa T, Iwakura Y, et al: IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med. 178:1023–1032. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Weaver CT, Harrington LE, Mangan PR, Gavrieli M and Murphy KM: Th17: An effector CD4 T cell lineage with regulatory T cell ties. Immunity. 24:677–688. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA and Cua DJ: IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 201:233–240. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ and Gurney AL: Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 278:1910–1914. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Huber M, Heink S, Grothe H, Guralnik A, Reinhard K, Elflein K, Hünig T, Mittrücker HW, Brüstle A, Kamradt T and Lohoff M: A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity. Eur J Immunol. 39:1716–1725. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Li K, Wang Z, Cao Y, Bunjhoo H, Zhu J, Chen Y, Xiong S, Xu Y and Xiong W: The study of the ratio and distribution of Th17 cells and Tc17 cells in asthmatic patients and the mouse model. Asian Pac J Allergy Immunol. 31:125–131. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Gong S, Li J, Ma L, Li K, Zhang L, Wang G, Liu Y, Ji X, Liu X, Chen P, et al: Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function. FEBS J. 280:6262–6273. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Khurana Hershey GK, Korfhagen TR, Hardie WD, Whitsett JA and Le Cras TD: Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol. 41:415–425. 2009. View Article : Google Scholar : PubMed/NCBI

21 

You QH, Zhang D, Niu CC, Zhu ZM, Wang N, Yue Y and Sun GY: Expression of IL-17A and IL-17F in lipopolysaccharide-induced acute lung injury and the counteraction of anisodamine or methylprednisolone. Cytokine. 66:78–86. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Sauer KA, Scholtes P, Karwot R and Finotto S: Isolation of CD4+ T cells from murine lungs: A method to analyze ongoing immune responses in the lung. Nat Protoc. 1:2870–2875. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Daubeuf F, Hachet-Haas M, Gizzi P, Gasparik V, Bonnet D, Utard V, Hibert M, Frossard N and Galzi JL: An antedrug of the CXCL12 neutraligand blocks experimental allergic asthma without systemic effect in mice. J Biol Chem. 288:11865–11876. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Heesen M, Berman MA, Höpken UE, Gerard NP and Dorf ME: Alternate splicing of mouse fusin/CXC chemokine receptor-4: Stromal cell-derived factor-1alpha is a ligand for both CXC chemokine receptor-4 isoforms. J Immunol. 158:3561–3564. 1997.PubMed/NCBI

25 

Weaver CT: Th17: The ascent of a new effector T-cell subset. Preface. Eur J Immunol. 39:634–636. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Yen HR, Harris TJ, Wada S, Grosso JF, Getnet D, Goldberg MV, Liang KL, Bruno TC, Pyle KJ, Chan SL, et al: Tc17 CD8 T cells: Functional plasticity and subset diversity. J Immunol. 183:7161–7168. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Yamashita N and Clement LT: Phenotypic characterization of the post-thymic differentiation of human alloantigen-specific CD8+ cytotoxic T lymphocytes. J Immunol. 143:1518–1523. 1989.PubMed/NCBI

28 

Zhao Y, Yang J and Gao YD: Altered expressions of helper T cell (Th)1, Th2, and Th17 cytokines in CD8(+) and γδ T cells in patients with allergic asthma. J Asthma. 48:429–436. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Oboki K, Ohno T, Saito H and Nakae S: Th17 and allergy. Allergol Int. 57:121–134. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Zhao Y, Balato A, Fishelevich R, Chapoval A, Mann DL and Gaspari AA: Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis. Br J Dermatol. 161:1301–1306. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen H, Xu X, Teng J, Cheng S, Bunjhoo H, Cao Y, Liu J, Xie J, Wang C, Xu Y, Xu Y, et al: CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response. Exp Ther Med 11: 1865-1870, 2016.
APA
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y. ... Xiong, W. (2016). CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response. Experimental and Therapeutic Medicine, 11, 1865-1870. https://doi.org/10.3892/etm.2016.3141
MLA
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y., Liu, J., Xie, J., Wang, C., Xu, Y., Xiong, W."CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response". Experimental and Therapeutic Medicine 11.5 (2016): 1865-1870.
Chicago
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y., Liu, J., Xie, J., Wang, C., Xu, Y., Xiong, W."CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1865-1870. https://doi.org/10.3892/etm.2016.3141
Copy and paste a formatted citation
x
Spandidos Publications style
Chen H, Xu X, Teng J, Cheng S, Bunjhoo H, Cao Y, Liu J, Xie J, Wang C, Xu Y, Xu Y, et al: CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response. Exp Ther Med 11: 1865-1870, 2016.
APA
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y. ... Xiong, W. (2016). CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response. Experimental and Therapeutic Medicine, 11, 1865-1870. https://doi.org/10.3892/etm.2016.3141
MLA
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y., Liu, J., Xie, J., Wang, C., Xu, Y., Xiong, W."CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response". Experimental and Therapeutic Medicine 11.5 (2016): 1865-1870.
Chicago
Chen, H., Xu, X., Teng, J., Cheng, S., Bunjhoo, H., Cao, Y., Liu, J., Xie, J., Wang, C., Xu, Y., Xiong, W."CXCR4 inhibitor attenuates ovalbumin-induced airway inflammation and hyperresponsiveness by inhibiting Th17 and Tc17 cell immune response". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1865-1870. https://doi.org/10.3892/etm.2016.3141
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