Effects of Quercetin Treatment on Epithelium-derived Cytokines and Epithelial Cell Apoptosis in Allergic Airway Inflammation Mice Model
-
Sule Caglayan Sozmen
,
Meral Karaman
,
Serap Cilaker Micili
,
Sakine Isik
,
Alper Bagriyanik
,
Zeynep Arikan Ayyildiz
,
Nevin Uzuner
,
Ozden Anal
,
Ozkan Karaman
Abstract
Quercetin is a dietary flavonoid which has anti-inflammatory effects. This study aimed to evaluate the influence of quercetin on histopathological aspects and airway epithelium in allergic airway inflammation mice model. Twenty-eight BALB/c mice were randomly divided into four groups: Group I (control), Group II (untreated mice with allergic airway inflammation), Group III (allergic airway inflammation quercetin-treated [16mg/kg/day]), Group IV (allergic airway inflammation dexamethasone-treated [1mg/kg/day]). Ovalbumin was administered intraperitoneally and via inhalation to achieve allergic airway inflammation mice model and treatments were also given intraperitoneally. Epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness were examined on samples isolated from lung. Immunohistochemical evaluationof lung tissues was performed using IL-25, IL-33, thymic stromal lymphopoietin (TSLP), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases(caspase)-3 antibodies. IL-4, IL-25, IL-33, TSLP were quantified in bronchoalveolar lavage (BAL) and OVAspecific IgE levels was measured in serum by standard ELISA protocols. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and cysteine-dependent aspartate-specific proteases (caspase)-3. Quercetin treatment led to lower epithelial thickness, subepithelial smooth muscle thickness, goblet and mast cell numbers compared to untreated mice with allergic airway inflammation (p<0.05). However, quercetin treatment was not effective on improving basal membane thickness. Immunohistochemical scores of IL-25, IL-33, TSLP, caspase-3 and TUNEL were lower in quercetin-treated mice t compared to untreated mice with allergic airway inflammation (p<0.05). IL-4, IL-25, IL-33, TSLP levels in BAL and OVA-specific IgE in serum were lower in quercetin treated mice compared to untreated mice (p<0.05). These findings suggest that quercetin improves chronic histopathological changes except basal membrane thickness in lung tissue and its beneficial effects on inflammation might be related to modulating epithelium derived cytokines and epithelial apoptosis.
1. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med 2012; 18(5):673-83.
2. Cho JY. Recent advances in mechanisms and treatments of airway remodeling in asthma: a message from the bench side to the clinic. Korean J Intern Med 2011; 26(4):367-83.
3. Park HJ, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, et al. Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol 2009; 9(3):261-7.
4. Olmez D, Babayigit A, Uzuner N, Erbil G, Karaman O, Yilmaz O, et al. Efficacy of sulphasalazine on lung histopathology in a murine model of chronic asthma. Exp Lung Res 2008;34(8):501-11.
5. Temelkovski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax 1998; 53(10):849-56.
6. Micili SC, Ergur BU, Ozogul C, Sarioglu S, Bagriyanik HA, Tugyan K, et al. Effects of lipoic acid in an experimentally induced hypertensive and diabetic rat model. Clin Exp Hypertens 2013;35(5):373-81.
7. Gencpinar P, Tuzun F, Ozbal S, Tugyan K, Duman N, Ozkan H, et al. Effects of neotrofin on neonatal Quercetin Treatment in Airway Inflammation Mice Model hypoxic ischemic brain injury. Neuroscience letters.2011;505(2):205-10.
8. Tuzun F, Gencpinar P, Ozbal S, Dilek M, Ergur BU, Duman N, et al. Neuroprotective effect of neotrofin in a neonatal rat model of periventricular leukomalacia. Neurosci Lett 2012; 520(1):6-10.
9. Hackett TL, Knight DA. The role of epithelial injury and repair in the origins of asthma. Curr Opin Allergy Clin Immunol 2007; 7(1):63-8.
10. Durrani SR, Viswanathan RK, Busse WW. What effect does asthma treatment have on airway remodeling? Current perspectives. J Allergy Clin Immunol 2011; 128(3):439-48.
11. Shale DJ, Ionescu AA. Mucus hypersecretion: a common symptom, a common mechanism? The Eur Respir J 2004; 23(6):797-8.
12. Liesker JJ, Ten Hacken NH, Zeinstra-Smith M, Rutgers SR, Postma DS, Timens W. Reticular basement membrane in asthma and COPD: similar thickness, yet different composition. Int J Chron Obstruct Pulmon Dis 2009; 4:127-35.
13. Bergeron C, Hauber HP, Gotfried M, Newman K, Dhanda R, Servi RJ, et al. Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: effect of hydrofluoroalkane- flunisolide. J Allergy Clin Immunol 2005;116(5):983-9.
14. Capraz F, Kunter E, Cermik H, Ilvan A, Pocan S.The effect of inhaled budesonide and formoterol on bronchial remodeling and HRCT features in young asthmatics. Lung 2007; 185(2):89-96.
15. Ward C, Pais M, Bish R, Reid D, Feltis B, Johns D, et al. Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002; 57(4):309-16.
16. Oliveira TT, Campos KM, Cerqueira-Lima AT, Cana Brasil Carneiro T, da Silva Velozo E, Ribeiro Melo IC, et al. Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. Daru 2015;23:18.
17. Rogerio AP, Dora CL, Andrade EL, Chaves JS, Silva LF, Lemos-Senna E, et al. Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol Res 2010; 61(4):288-97.
18. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol 2010; 10(4):225-35.
19. KleinJan A. Airway inflammation in asthma: key players beyond the Th2 pathway. Curr Opin Pulm Med 2016; 22(1):46-52.
20. Barlow JL, Peel S, Fox J, Panova V, Hardman CS,Camelo A, et al. IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J Allergy Clin Immunol 2013; 132(4):933-41.
21. Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK. IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol 2008;180(4):2443-9.
22. Trautmann A, Schmid-Grendelmeier P, Kruger K, Crameri R, Akdis M, Akkaya A, et al. T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma. J Allergy Clin Immunol 2002; 109(2):329-37.
23. Penberthy KK, Juncadella IJ, Ravichandran KS.Apoptosis and engulfment by bronchial epithelial cells. Implications for allergic airway inflammation. Ann Am Thorac Soc 2014; 11(Suppl 5):S259-62.
24. Arnett HA, Viney JL. Considerations for the sensible use of rodent models of inflammatory disease in predicting efficacy of new biological therapeutics in the clinic. Adv Drug Deliv Rev 2007; 59(11):1084-92.
25. Chen L, Grabowski KA, Xin JP, Coleman J, Huang Z, Espiritu B, et al. IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils. J Immunol 2004; 172(4):2059-66.
| Files | ||
| Issue | Vol 15, No 6 (2016) | |
| Section | Original Article(s) | |
| Keywords | ||
| Allergic airway inflammation Antiinflammatory effects Mouse model Quercetin | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
