Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin–dendritic Cell–OX40 Ligand Axis in a Mouse Model
-
Wen Cui
,
Huan Zhou
,
Ya-zun Liu
,
Yan Yang
,
Yi-zhong Hu
,
Zhao-peng Han
,
Jian-er Yu
,
Zheng Xue
Abstract
Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)–dendritic cell (DC)–OX40L axis was investigated.
A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively.
Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased.
Amygdalin thus regulates the Th1/Th2 balance through the TSLP–DC–OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.
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19. Xue Z, Zhang XG, Wu J, Xu WC, Li LQ, Liu F, et al. Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice. Ann Allergy Asthma Immunol. 2016;116(6):506-13.
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23. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45-56.
24. Casaro M, Souza VR, Oliveira FA, Ferreira CM. OVA-induced allergic airway inflammation mouse model. Methods Mol Biol. 2019;1916:297-301.
25. Fujio K, Nosaka T, Kojima T, Kawashima T, Yahata T, Copeland NG, et al. Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood. 2000;95(7):2204-10.
26. Kitajima M, Lee HC, Nakayama T, Ziegler SF. TSLP enhances the function of helper type 2 cells. Eur J Immunol. 2011;41(7):1862-71.
27. Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777-92.
28. West EE, Kashyap M, Leonard WJ. TSLP: A key regulator of asthma pathogenesis. Drug Discov Today Dis Mech. 2012;9(3-4):10.1016/j.ddmec.2012.09.003.
29. Ziegler SF. The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol. 2010;22(6):795-9.
30. Boonpiyathad T, Sozener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019;46:101333.
31. Lombardi V, Singh AK, Akbari O. The role of costimulatory molecules in allergic disease and asthma. Int Arch Allergy Immunol. 2010;151(3):179-89.
32. Lofdahl JM, Wahlstrom J, Skold CM. Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and non-smokers. Clin Exp Immunol. 2006;145(3):428-37.
33. Liu YJ, Soumelis V, Watanabe N, Ito T, Wang YH, Malefyt Rde W, et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu Rev Immunol. 2007;25:193-219.
34. Gu W, Guo S, Zhang J, Zhang X, Sun Z, Chen Z, et al. March1-overexpressed dendritic cells downregulate Th1/Th2 ratio in asthma through promoting OX40L. Int Immunopharmacol. 2022;103:108444.
35. Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134(3):671-8.e4.
36. Russkamp D, Aguilar-Pimentel A, Alessandrini F, Gailus-Durner V, Fuchs H, Ohnmacht C, et al. IL-4 receptor alpha blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma. Allergy. 2019;74(8):1549-60.
37. Eifan AO, Furukido K, Dumitru A, Jacobson MR, Schmidt-Weber C, Banfield G, et al. Reduced T-bet in addition to enhanced STAT6 and GATA3 expressing T cells contribute to human allergen-induced late responses. Clin Exp Allergy. 2012;42(6):891-900.
2. de Vreede I, Haarman EG, Sprikkelman AB, van Aalderen WM. From knemometry to final adult height: inhaled corticosteroids and their effect on growth in childhood. Paediatr Respir Rev. 2013;14(2):107-11; quiz 11, 137-8.
3. Heffler E, Madeira LNG, Ferrando M, Puggioni F, Racca F, Malvezzi L, et al. Inhaled corticosteroids safety and adverse effects in patients with asthma. J Allergy Clin Immunol Pract. 2018;6(3):776-81.
4. Lindsay JT, Heaney LG. Nonadherence in difficult asthma- facts, myths, and a time to act. Patient Prefer Adherence. 2013;7:329-36.
5. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469-85.
6. Han X, Krempski JW, Nadeau K. Advances and novel developments in mechanisms of allergic inflammation. Allergy. 2020;75(12):3100-11.
7. Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013-21.
8. Guttman-Yassky E, Pavel AB, Zhou L, Estrada YD, Zhang N, Xu H, et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;144(2):482-93.
9. Morianos I, Semitekolou M. Dendritic cells: Critical regulators of allergic asthma. Int J Mol Sci. 2020;21(21):7930.
10. Corren J, Ziegler SF. TSLP: from allergy to cancer. Nat Immunol. 2019;20(12):1603-9.
11. Murakami-Satsutani N, Ito T, Nakanishi T, Inagaki N, Tanaka A, Vien PTX, et al. IL-33 Promotes the induction and maintenance of Th2 immune responses by enhancing the function of OX40 ligand. Allergol Int. 2014;63(3):
443-55.
12. Feng S, Zhang L, Bian XH, Luo Y, Qin GH, Shi RM. Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice. Biochem Cell Biol. 2018;96(3):306-16.
13. Nyanhanda T, Gould EM, Hurst RD. Plant-derived foods for the attenuation of allergic airway inflammation. Curr Pharm Des. 2014;20(6):869-78.
14. Coleman SL, Shaw OM. Progress in the understanding of the pathology of allergic asthma and the potential of fruit proanthocyanidins as modulators of airway inflammation. Food Funct. 2017;8(12):4315-24.
15. Piao X, Jiang SH, Wang JN, Wu J, Xu WC, Li LQ, et al. Pingchuan formula attenuates airway mucus hypersecretion via regulation of the PNEC-GABA-IL13-Muc5ac axis in asthmatic mice. Biomed Pharmacother. 2021;140:111746.
16. Shi J, Chen Q, Xu M, Xia Q, Zheng T, Teng J, et al. Recent updates and future perspectives about amygdalin as a potential anticancer agent: A review. Cancer Med. 2019;8(6):3004-11.
17. He XY, Wu LJ, Wang WX, Xie PJ, Chen YH, Wang F. Amygdalin - A pharmacological and toxicological review. J Ethnopharmacol. 2020;254:112717.
18. Si Z, Zhang B. Amygdalin attenuates airway epithelium apoptosis, inflammation, and epithelial-mesenchymal transition through restraining the TLR4/NF-B signaling pathway on LPS-treated BEAS-2B bronchial epithelial cells. Int Arch Allergy Immunol. 2021;182(10):997-1007.
19. Xue Z, Zhang XG, Wu J, Xu WC, Li LQ, Liu F, et al. Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice. Ann Allergy Asthma Immunol. 2016;116(6):506-13.
20. Castro-Rodriguez JA, Saglani S, Rodriguez-Martinez CE, Oyarzun MA, Fleming L, Bush A. The relationship between inflammation and remodeling in childhood asthma: A systematic review. Pediatr Pulmonol. 2018;53(6):824-35.
21. Janssen LJ, Killian K. Airway smooth muscle as a target of asthma therapy: history and new directions. Respir Res. 2006;7:123.
22. Lam M, Royce SG, Samuel CS, Bourke JE. Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases. Pharmacol Ther. 2018;187:61-70.
23. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45-56.
24. Casaro M, Souza VR, Oliveira FA, Ferreira CM. OVA-induced allergic airway inflammation mouse model. Methods Mol Biol. 2019;1916:297-301.
25. Fujio K, Nosaka T, Kojima T, Kawashima T, Yahata T, Copeland NG, et al. Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain. Blood. 2000;95(7):2204-10.
26. Kitajima M, Lee HC, Nakayama T, Ziegler SF. TSLP enhances the function of helper type 2 cells. Eur J Immunol. 2011;41(7):1862-71.
27. Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777-92.
28. West EE, Kashyap M, Leonard WJ. TSLP: A key regulator of asthma pathogenesis. Drug Discov Today Dis Mech. 2012;9(3-4):10.1016/j.ddmec.2012.09.003.
29. Ziegler SF. The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol. 2010;22(6):795-9.
30. Boonpiyathad T, Sozener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019;46:101333.
31. Lombardi V, Singh AK, Akbari O. The role of costimulatory molecules in allergic disease and asthma. Int Arch Allergy Immunol. 2010;151(3):179-89.
32. Lofdahl JM, Wahlstrom J, Skold CM. Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and non-smokers. Clin Exp Immunol. 2006;145(3):428-37.
33. Liu YJ, Soumelis V, Watanabe N, Ito T, Wang YH, Malefyt Rde W, et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu Rev Immunol. 2007;25:193-219.
34. Gu W, Guo S, Zhang J, Zhang X, Sun Z, Chen Z, et al. March1-overexpressed dendritic cells downregulate Th1/Th2 ratio in asthma through promoting OX40L. Int Immunopharmacol. 2022;103:108444.
35. Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134(3):671-8.e4.
36. Russkamp D, Aguilar-Pimentel A, Alessandrini F, Gailus-Durner V, Fuchs H, Ohnmacht C, et al. IL-4 receptor alpha blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma. Allergy. 2019;74(8):1549-60.
37. Eifan AO, Furukido K, Dumitru A, Jacobson MR, Schmidt-Weber C, Banfield G, et al. Reduced T-bet in addition to enhanced STAT6 and GATA3 expressing T cells contribute to human allergen-induced late responses. Clin Exp Allergy. 2012;42(6):891-900.
| Files | ||
| Issue | Vol 22 No 5 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i5.13993 | |
| Keywords | ||
| Airway inflammation Amygdalin Asthma Dendritic cells OX40 ligand Th1-Th2 balance Thymic stromal lymphopoietin | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Cui W, Zhou H, Liu Y- zun, Yang Y, Hu Y- zhong, Han Z- peng, Yu J- er, Xue Z. Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin–dendritic Cell–OX40 Ligand Axis in a Mouse Model. Iran J Allergy Asthma Immunol. 2023;22(5):430-439.
