Skip to main content
Erschienen in: Inflammation 3/2020

14.01.2020 | Original Article

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model

verfasst von: Xiang-Qian Luo, Jian-Wen Zhong, Shu-Yao Qiu, Min Zhi, Li-Qiang Yang, Yi-Long Zhou, Fen-Xuan Zhou, Ping-Chang Yang, Da-Bo Liu, Li-Hua Mo

Erschienen in: Inflammation | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.
Literatur
1.
Zurück zum Zitat Masoli, M., D. Fabian, S. Holt, and R. Beasley. 2004. The global burden of asthma: Executive summary of the GINA DisSDination Committee report. Allergy. 59: 469–478.CrossRef Masoli, M., D. Fabian, S. Holt, and R. Beasley. 2004. The global burden of asthma: Executive summary of the GINA DisSDination Committee report. Allergy. 59: 469–478.CrossRef
2.
Zurück zum Zitat Hirose, K., A. Iwata, T. Tamachi, and H. Nakajima. 2017. Allergic airway inflammation: Key players beyond the Th2 cell pathway. Immunological Reviews 278: 145–161.CrossRef Hirose, K., A. Iwata, T. Tamachi, and H. Nakajima. 2017. Allergic airway inflammation: Key players beyond the Th2 cell pathway. Immunological Reviews 278: 145–161.CrossRef
3.
Zurück zum Zitat Foster, P.S., S. Maltby, H.F. Rosenberg, H.L. Tay, S.P. Hogan, A.M. Collison, et al. 2017. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunological Reviews 278: 20–40.CrossRef Foster, P.S., S. Maltby, H.F. Rosenberg, H.L. Tay, S.P. Hogan, A.M. Collison, et al. 2017. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunological Reviews 278: 20–40.CrossRef
4.
Zurück zum Zitat Akdis, M., and C.A. Akdis. 2009. Therapeutic manipulation of immune tolerance in allergic disease. Nature Reviews. Drug Discovery 8: 645–660.CrossRef Akdis, M., and C.A. Akdis. 2009. Therapeutic manipulation of immune tolerance in allergic disease. Nature Reviews. Drug Discovery 8: 645–660.CrossRef
5.
Zurück zum Zitat Akdis, C.A. 2012. Therapies for allergic inflammation: Refining strategies to induce tolerance. Nature Medicine 18: 736–749.CrossRef Akdis, C.A. 2012. Therapies for allergic inflammation: Refining strategies to induce tolerance. Nature Medicine 18: 736–749.CrossRef
6.
Zurück zum Zitat Akdis, C.A., T. Blesken, M. Akdis, B. Wuthrich, and K. Blaser. 1998. Role of interleukin 10 in specific immunotherapy. The Journal of Clinical Investigation 102: 98–106.CrossRef Akdis, C.A., T. Blesken, M. Akdis, B. Wuthrich, and K. Blaser. 1998. Role of interleukin 10 in specific immunotherapy. The Journal of Clinical Investigation 102: 98–106.CrossRef
7.
Zurück zum Zitat Akkoc, T., D. Genc, N. Zibandeh, and T. Akkoc. 2018. Intranasal ovalbumin immunotherapy with mycobacterial adjuvant promotes regulatory T cell accumulation in lung tissues. Microbiology and Immunology 62: 531–540.CrossRef Akkoc, T., D. Genc, N. Zibandeh, and T. Akkoc. 2018. Intranasal ovalbumin immunotherapy with mycobacterial adjuvant promotes regulatory T cell accumulation in lung tissues. Microbiology and Immunology 62: 531–540.CrossRef
8.
Zurück zum Zitat Globinska, A., T. Boonpiyathad, P. Satitsuksanoa, M. Kleuskens, W. van de Veen, M. Sokolowska, et al. 2018. Mechanisms of allergen-specific immunotherapy: Diverse mechanisms of immune tolerance to allergens. Annals of Allergy, Asthma & Immunology 121: 306–312.CrossRef Globinska, A., T. Boonpiyathad, P. Satitsuksanoa, M. Kleuskens, W. van de Veen, M. Sokolowska, et al. 2018. Mechanisms of allergen-specific immunotherapy: Diverse mechanisms of immune tolerance to allergens. Annals of Allergy, Asthma & Immunology 121: 306–312.CrossRef
9.
Zurück zum Zitat Yukselen, A., and S.G. Kendirli. 2014. Role of immunotherapy in the treatment of allergic asthma. World Journal of Clinical Cases 2: 859–865.CrossRef Yukselen, A., and S.G. Kendirli. 2014. Role of immunotherapy in the treatment of allergic asthma. World Journal of Clinical Cases 2: 859–865.CrossRef
10.
Zurück zum Zitat Ma, A., and B.A. Malynn. 2012. A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nature Reviews. Immunology 12: 774–785.CrossRef Ma, A., and B.A. Malynn. 2012. A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nature Reviews. Immunology 12: 774–785.CrossRef
11.
Zurück zum Zitat Huang, P., X.R. Geng, G. Yang, C. Chen, Z. Liu, and P.C. Yang. 2012. Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function. Cellular Physiology and Biochemistry 30: 702–710.CrossRef Huang, P., X.R. Geng, G. Yang, C. Chen, Z. Liu, and P.C. Yang. 2012. Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function. Cellular Physiology and Biochemistry 30: 702–710.CrossRef
12.
Zurück zum Zitat Ventura, S., F. Cano, Y. Kannan, F. Breyer, M.J. Pattison, M.S. Wilson, and S.C. Ley. 2018. A20-binding inhibitor of NF-kappaB (ABIN) 2 negatively regulates allergic airway inflammation. The Journal of Experimental Medicine 215: 2737–2747.CrossRef Ventura, S., F. Cano, Y. Kannan, F. Breyer, M.J. Pattison, M.S. Wilson, and S.C. Ley. 2018. A20-binding inhibitor of NF-kappaB (ABIN) 2 negatively regulates allergic airway inflammation. The Journal of Experimental Medicine 215: 2737–2747.CrossRef
13.
Zurück zum Zitat Kang, N.I., H.Y. Yoon, Y.R. Lee, M. Won, M.J. Chung, J.W. Park, et al. 2009. A20 attenuates allergic airway inflammation in mice. Journal of Immunology 183: 1488–1495.CrossRef Kang, N.I., H.Y. Yoon, Y.R. Lee, M. Won, M.J. Chung, J.W. Park, et al. 2009. A20 attenuates allergic airway inflammation in mice. Journal of Immunology 183: 1488–1495.CrossRef
14.
Zurück zum Zitat Schuijs, M.J., M.A. Willart, K. Vergote, D. Gras, K. Deswarte, M.J. Ege, F.B. Madeira, R. Beyaert, G. van Loo, F. Bracher, E. von Mutius, P. Chanez, B.N. Lambrecht, and H. Hammad. 2015. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science. 349: 1106–1110.CrossRef Schuijs, M.J., M.A. Willart, K. Vergote, D. Gras, K. Deswarte, M.J. Ege, F.B. Madeira, R. Beyaert, G. van Loo, F. Bracher, E. von Mutius, P. Chanez, B.N. Lambrecht, and H. Hammad. 2015. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science. 349: 1106–1110.CrossRef
15.
Zurück zum Zitat Salari, F., A.R. Varasteh, F. Vahedi, M. Hashemi, and M. Sankian. 2015. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice. International Immunopharmacology 29: 672–678.CrossRef Salari, F., A.R. Varasteh, F. Vahedi, M. Hashemi, and M. Sankian. 2015. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice. International Immunopharmacology 29: 672–678.CrossRef
16.
Zurück zum Zitat Joshi, V.B., A. Adamcakova-Dodd, X. Jing, A. Wongrakpanich, K.N. Gibson-Corley, P.S. Thorne, and A.K. Salem. 2014. Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy. The AAPS Journal 16: 975–985.CrossRef Joshi, V.B., A. Adamcakova-Dodd, X. Jing, A. Wongrakpanich, K.N. Gibson-Corley, P.S. Thorne, and A.K. Salem. 2014. Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy. The AAPS Journal 16: 975–985.CrossRef
17.
Zurück zum Zitat Trindade, R.A., P.K. Kiyohara, P.S. de Araujo, and D.C.M. Bueno. 2012. PLGA microspheres containing bee venom proteins for preventive immunotherapy. International Journal of Pharmaceutics 423: 124–133.CrossRef Trindade, R.A., P.K. Kiyohara, P.S. de Araujo, and D.C.M. Bueno. 2012. PLGA microspheres containing bee venom proteins for preventive immunotherapy. International Journal of Pharmaceutics 423: 124–133.CrossRef
18.
Zurück zum Zitat Bosnjak, B., B. Stelzmueller, K.J. Erb, and M.M. Epstein. 2011. Treatment of allergic asthma: Modulation of Th2 cells and their responses. Respiratory Research 12: 114.CrossRef Bosnjak, B., B. Stelzmueller, K.J. Erb, and M.M. Epstein. 2011. Treatment of allergic asthma: Modulation of Th2 cells and their responses. Respiratory Research 12: 114.CrossRef
19.
Zurück zum Zitat Kim, S.B., A.Y. Lee, J.M. Chun, A.R. Lee, H.S. Kim, Y.S. Seo, et al. 2019. Anthriscus sylvestris root extract reduces allergic lung inflammation by regulating interferon regulatory factor 4-mediated Th2 cell activation. Journal of Ethnopharmacology 232: 165–175.CrossRef Kim, S.B., A.Y. Lee, J.M. Chun, A.R. Lee, H.S. Kim, Y.S. Seo, et al. 2019. Anthriscus sylvestris root extract reduces allergic lung inflammation by regulating interferon regulatory factor 4-mediated Th2 cell activation. Journal of Ethnopharmacology 232: 165–175.CrossRef
20.
Zurück zum Zitat Youm, J., H. Lee, H.B. Chang, J. Jeon, M.H. Yoon, J.Y. Woo, M.S. Choi, Y. Hwang, S. Seong, K. Na, and J. Yoon. 2017. Justicia procumbens extract (DW2008) selectively suppresses Th2 cytokines in splenocytes and ameliorates ovalbumin-induced airway inflammation in a mouse model of asthma. Biological & Pharmaceutical Bulletin 40: 1416–1422.CrossRef Youm, J., H. Lee, H.B. Chang, J. Jeon, M.H. Yoon, J.Y. Woo, M.S. Choi, Y. Hwang, S. Seong, K. Na, and J. Yoon. 2017. Justicia procumbens extract (DW2008) selectively suppresses Th2 cytokines in splenocytes and ameliorates ovalbumin-induced airway inflammation in a mouse model of asthma. Biological & Pharmaceutical Bulletin 40: 1416–1422.CrossRef
21.
Zurück zum Zitat Luo, X.Q., F. Ma, S. Wang, M.Z. Zhao, J.B. Shao, X.R. Geng, et al. 2019. Interleukin-5 induces apoptotic defects in CD4(+) T cells of patients with allergic rhinitis. Journal of Leukocyte Biology 105: 719–727.CrossRef Luo, X.Q., F. Ma, S. Wang, M.Z. Zhao, J.B. Shao, X.R. Geng, et al. 2019. Interleukin-5 induces apoptotic defects in CD4(+) T cells of patients with allergic rhinitis. Journal of Leukocyte Biology 105: 719–727.CrossRef
22.
Zurück zum Zitat De Jong, W.H., and P.J. Borm. 2008. Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine 3: 133–149.CrossRef De Jong, W.H., and P.J. Borm. 2008. Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine 3: 133–149.CrossRef
23.
Zurück zum Zitat Choi, S., J. Lee, P. Kumar, K.Y. Lee, and S.K. Lee. 2011. Single chain variable fragment CD7 antibody conjugated PLGA/HDAC inhibitor immuno-nanoparticles: Developing human T cell-specific nano-technology for delivery of therapeutic drugs targeting latent HIV. Journal of Control Release 152 (Suppl 1): e9–e10.CrossRef Choi, S., J. Lee, P. Kumar, K.Y. Lee, and S.K. Lee. 2011. Single chain variable fragment CD7 antibody conjugated PLGA/HDAC inhibitor immuno-nanoparticles: Developing human T cell-specific nano-technology for delivery of therapeutic drugs targeting latent HIV. Journal of Control Release 152 (Suppl 1): e9–e10.CrossRef
24.
Zurück zum Zitat Reddy, K.S., B.R. Rashmi, H.J. Dechamma, S. Gopalakrishna, N. Banumathi, V.V. Suryanarayana, et al. 2012. Cationic microparticle [poly(D,L-lactide-co-glycolide)]-coated DNA vaccination induces a long-term immune response against foot and mouth disease in guinea pigs. The Journal of Gene Medicine 14: 348–352.CrossRef Reddy, K.S., B.R. Rashmi, H.J. Dechamma, S. Gopalakrishna, N. Banumathi, V.V. Suryanarayana, et al. 2012. Cationic microparticle [poly(D,L-lactide-co-glycolide)]-coated DNA vaccination induces a long-term immune response against foot and mouth disease in guinea pigs. The Journal of Gene Medicine 14: 348–352.CrossRef
25.
Zurück zum Zitat Kostadinova, A.I., J. Middelburg, M. Ciulla, J. Garssen, W.E. Hennink, L. Knippels, C. van Nostrum, and L.E.M. Willemsen. 2018. PLGA nanoparticles loaded with beta-lactoglobulin-derived peptides modulate mucosal immunity and may facilitate cow’s milk allergy prevention. European Journal of Pharmacology 818: 211–220.CrossRef Kostadinova, A.I., J. Middelburg, M. Ciulla, J. Garssen, W.E. Hennink, L. Knippels, C. van Nostrum, and L.E.M. Willemsen. 2018. PLGA nanoparticles loaded with beta-lactoglobulin-derived peptides modulate mucosal immunity and may facilitate cow’s milk allergy prevention. European Journal of Pharmacology 818: 211–220.CrossRef
26.
Zurück zum Zitat Khademi, F., M. Derakhshan, A. Yousefi-Avarvand, A. Najafi, and M. Tafaghodi. 2018. A novel antigen of mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity. Microbial Pathogenesis 125: 507–513.CrossRef Khademi, F., M. Derakhshan, A. Yousefi-Avarvand, A. Najafi, and M. Tafaghodi. 2018. A novel antigen of mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity. Microbial Pathogenesis 125: 507–513.CrossRef
27.
Zurück zum Zitat Sadat, T.M.F., K. Nejati-Koshki, A. Akbarzadeh, M.R. Yamchi, M. Milani, N. Zarghami, et al. 2014. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific Journal of Cancer Prevention 15: 517–535.CrossRef Sadat, T.M.F., K. Nejati-Koshki, A. Akbarzadeh, M.R. Yamchi, M. Milani, N. Zarghami, et al. 2014. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific Journal of Cancer Prevention 15: 517–535.CrossRef
28.
Zurück zum Zitat Matsuda, M., Y. Morie, H. Oze, K. Doi, T. Tsutsumi, J. Hamaguchi, M. Inaba, and T. Nabe. 2018. Phenotype analyses of IL-10-producing Foxp3(-) CD4(+) T cells increased by subcutaneous immunotherapy in allergic airway inflammation. International Immunopharmacology 61: 297–305.CrossRef Matsuda, M., Y. Morie, H. Oze, K. Doi, T. Tsutsumi, J. Hamaguchi, M. Inaba, and T. Nabe. 2018. Phenotype analyses of IL-10-producing Foxp3(-) CD4(+) T cells increased by subcutaneous immunotherapy in allergic airway inflammation. International Immunopharmacology 61: 297–305.CrossRef
29.
Zurück zum Zitat Bohm, L., J. Maxeiner, H. Meyer-Martin, S. Reuter, S. Finotto, M. Klein, et al. 2015. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma. Journal of Immunology 194: 887–897.CrossRef Bohm, L., J. Maxeiner, H. Meyer-Martin, S. Reuter, S. Finotto, M. Klein, et al. 2015. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma. Journal of Immunology 194: 887–897.CrossRef
Metadaten
Titel
A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model
verfasst von
Xiang-Qian Luo
Jian-Wen Zhong
Shu-Yao Qiu
Min Zhi
Li-Qiang Yang
Yi-Long Zhou
Fen-Xuan Zhou
Ping-Chang Yang
Da-Bo Liu
Li-Hua Mo
Publikationsdatum
14.01.2020
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 3/2020
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-020-01181-5

Weitere Artikel der Ausgabe 3/2020

Inflammation 3/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.