Study Effect of Vitamin D on the Immunopathology Responses of the Bronchi in Murine Model of Asthma
,
Abstract
Allergic asthma is a complicated respiratory problem characterized by airway inflammation, airway hyperresponsiveness (AHR), breathlessness, mucus hyper-secretion, and goblet cell hyperplasia. Asthma is controlled by genetic and environmental factors. Allergy is the main trigger of asthma and is mediated by Th2 cytokines along with IgE production. Vitamin D (Vit D) is the main supplementary factor for the immune system. In the present study, we investigated the effect of Vit D on the exacerbation of allergic asthma.
A murine model of allergic asthma was induced by ovalbumin (OVA) in four of five groups of studied female BALB/c mice (each group, n=20). One group was considered as control. Of OVA-induced mice, two groups received Vit D via oral (10,000 IU/kg diet) or intranasal (inhalation) forms (30 min on days 25, 27, and 29), and the third group received budesonide. At least, AHR, the levels of IL-4, IL-5, IL-13, and INF-g in bronchoalveolar lavage fluid (BALF), serum IgE and histamine, IL-25 and IL-33 gene expression, as well as histopathology study of the lung were done.
The Penh values, type2 Cytokines in BALF (in both protein and molecular levels), total IgE and histamine, perivascular and peribronchial inflammation, goblet cell hyperplasia, and mucus hypersecretion decreased significantly in both oral and intranasal Vit D-treated asthmatic mice groups, especially on day 38 of orally treated mice.
Here, we found Vit D as a promising agent in control of allergic asthma with a remarkable ability to decrease the severity of inflammation. Therefore, Vit D sufficiency is highly recommended in asthmatic patients.
1. Athari SS. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther. 2019; 4:45.
2. Athari SS, Pourpak Z, Folkerts G, Garssen J et al. Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice. Eur J Pharmacol. 2016; 15(791):811-820.
3. Athari SS, Athari SM, Beyzay F, Movassaghi M, Mortaz E, Taghavi M. Critical role of Toll-like receptors in pathophysiology of allergic asthma. Eur J Pharmacol. 2017; 808(4):21-27
4. Athari SM, Mehrabi Nasab E, Athari SS. Study effect of Ocimumbasilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue Française d'Allergologie. 2018; 58(7):489-93
5. Mirzakhani H, Amal Al-Garawi, Scott T. Weiss and Augusto A. Litonjua. Vitamin D and the development of allergic disease: how important is it? Clin Exp Allergy. 2015; 45(1) 114-25
6. Litonjua, A. The Role of Vitamin D in the Development, Exacerbation, and Severity of Asthma and Allergic Diseases. Vitamin D and the Lung: Mechanisms and Disease Associations. In: Litonjua, AA, editor. Respiratory Med. 2012; 3(2):201-38.
7. Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013; 88(7):720–55.
8. Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, Uskokovic M. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004;89–90(1-5):437–41.
9. Pichler J, Gerstmayr M, Szepfalusi Z, Urbanek R, Peterlik M, Willheim M. 1 alpha,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells. PediatrRes. 2002; 52(1):12–8.
10. Kimberly D. Fischer, Sannette C. Hall and Devendra K. Agrawal. Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice. PLoS One. 2016;11(2):e0149180.
11. Paul E. Pfeffer, Elizabeth H. Mann, Eve Hornsby, Emma S. Chambers, Yin-Huai Chen, Louise Rice, and Catherine M. Hawrylowicz. Vitamin D Influences Asthmatic Pathology through Its Action on Diverse Immunological Pathways. Ann Am Thorac Soc. 2014;11( 5):S314-320
12. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017;85(14):78–97.
13. Bscheider M, Butcher EC. Vitamin D immunoregulation through dendritic cells. Immunology. 2016;148(3):227–36.
14. Tanupriya Agrawal, Gaurav K. Gupta, and Devendra K. Agrawal. Vitamin D Supplementation Reduces Airway Hyperresponsiveness and Allergic Airway Inflammation in a Murine Model. Clin Exp Allergy. 2013;43(6):672–83.
15. Karin Hufnagl • Erika Jensen-Jarolim. Vitamin A and D in allergy: from experimental animal models and cellular studies to human disease. Allergo J Int. 2018;27(3):72–8
16. Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015;7(4):3011–21.
17. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effectsof 1,25-dihydroxyvitaminD3onhuman Bcelldifferentiation. J Immunol. 2007;179(3):1634–47.
18. Mak G, Hanania NA: Vitamin D and asthma. CurrOpinPulm Med. 2011;17(1):1–5.
19. Chambers ES, Hawrylowicz CM: The impact of vitamin D on regulatory T cells. Curr Allergy Asthma Rep. 2011;11(1):29–36.
20. Brehm JM, Schuemann B, Fuhlbrigge AL, et al.: Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010;126(1):52–8.
21. Ali N S, Nanji K. A Review on the Role of Vitamin D in Asthma. Cureus. 2017;9(5):e1288.
22. Hollams EM, Hart PH, Holt BJ, et al.: Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011;38(6):1320–7
23. Freishtat RJ, Iqbal SF, Pillai DK, et al.: High prevalence of vitamin D deficiency among innercity African American youth with asthma in Washington, DC. J Pediatr. 2010;156(6):948–52.
24. Chinellato I, Piazza M, Sandri M, et al.: Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr. 2011;158(3):437–41.
25. Devereux G, Wilson A, Avenell A, et al.: A case-control study of vitamin D status and asthma in adults. Allergy. 2014;65(5):666–7
26. Camargo CA, Ingham T, Wickens K, et al.: Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127(1):180–7.
27. FemkeBaeke, Tatiana Takiishi, Hannelie Korf, Conny Gysemans, Chantal Mathieu. Vitamin D: modulator of the immune system. CurrOpinPharmacol; 2010;10(4):482-96.
28. Shahin MYA, El-lawah AA, Amin A, et al.: Study of serum vitamin D level in adult patients with bronchial asthma. Egypt J Chest Dis Tuberc. 2017;66(1):5-9.
29. Kho, Alvin T, Sunita Sharma, WeiliangQiu, Roger Gaedigk, Barbara Klanderman, SiminNiu, Chris Anderson, James S Leeder, Scott T Weiss, and Kelan G Tantisira. Vitamin D related genes in lung development and asthma pathogenesis. BMC Med Genomics. 2013;6(1):47.
30. Marin L, Dufour ME, Nguyen TM, Tordet C, Garabedian M. Maturational changes induced by 1 alpha,25-dihydroxyvitamin D3 in type II cells from fetal rat lung explants. Am J Physiol. 1993; 265(1 pt 1):L45–52.
31. Xystrakis E, Kusumakar S, Boswell S, Peek E, Urry Z, Richards DF, Adikibi T, Pridgeon C, Dallman M, Loke TK, Robinson DS, Barrat FJ, O’Garra A, Lavender P, Lee TH, Corrigan C, Hawrylowicz CM. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest. 2006;116(1):146–55.
32. Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127(5):1294–6.
33. Li F, Peng M, Jiang L, Sun Q, Zhang K, Lian F, Litonjua AA, Gao J, Gao X. Vitamin D deficiency is associated with decreased lung function in Chinese adults with asthma. Respiration. 2011; 81(6):469–75.
34. Bosse Y, Maghni K, Hudson TJ. 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes. PhysiolGenomics. 2007; 29(2):161–8.
35. Wang Z, Zhang H, Sun X, Ren L. The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-beta/Smad signaling and activation of theNrf2/HO-1 pathway. Mol Med Rep. 2016;14(3):2389–96.
36. David A Jolliffe, Lauren Greenberg, Richard L Hooper, Christopher J Griffiths, Carlos A Camargo Jr, Conor P Kerley, Megan E Jensen, David Mauger, Iwona Stelmach, Mitsuyoshi Urashima, Adrian R Martineau. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet Respir Med. 2017;5(11):881–90
37. Liu ZQ, Li XX, Qiu SQ, Yu Y, Li MG, Yang LT, et al. Vitamin D contributes to mast cell stabilization. Allergy. 2017;72(8):1184–92.
2. Athari SS, Pourpak Z, Folkerts G, Garssen J et al. Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice. Eur J Pharmacol. 2016; 15(791):811-820.
3. Athari SS, Athari SM, Beyzay F, Movassaghi M, Mortaz E, Taghavi M. Critical role of Toll-like receptors in pathophysiology of allergic asthma. Eur J Pharmacol. 2017; 808(4):21-27
4. Athari SM, Mehrabi Nasab E, Athari SS. Study effect of Ocimumbasilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue Française d'Allergologie. 2018; 58(7):489-93
5. Mirzakhani H, Amal Al-Garawi, Scott T. Weiss and Augusto A. Litonjua. Vitamin D and the development of allergic disease: how important is it? Clin Exp Allergy. 2015; 45(1) 114-25
6. Litonjua, A. The Role of Vitamin D in the Development, Exacerbation, and Severity of Asthma and Allergic Diseases. Vitamin D and the Lung: Mechanisms and Disease Associations. In: Litonjua, AA, editor. Respiratory Med. 2012; 3(2):201-38.
7. Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013; 88(7):720–55.
8. Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, Uskokovic M. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004;89–90(1-5):437–41.
9. Pichler J, Gerstmayr M, Szepfalusi Z, Urbanek R, Peterlik M, Willheim M. 1 alpha,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells. PediatrRes. 2002; 52(1):12–8.
10. Kimberly D. Fischer, Sannette C. Hall and Devendra K. Agrawal. Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice. PLoS One. 2016;11(2):e0149180.
11. Paul E. Pfeffer, Elizabeth H. Mann, Eve Hornsby, Emma S. Chambers, Yin-Huai Chen, Louise Rice, and Catherine M. Hawrylowicz. Vitamin D Influences Asthmatic Pathology through Its Action on Diverse Immunological Pathways. Ann Am Thorac Soc. 2014;11( 5):S314-320
12. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017;85(14):78–97.
13. Bscheider M, Butcher EC. Vitamin D immunoregulation through dendritic cells. Immunology. 2016;148(3):227–36.
14. Tanupriya Agrawal, Gaurav K. Gupta, and Devendra K. Agrawal. Vitamin D Supplementation Reduces Airway Hyperresponsiveness and Allergic Airway Inflammation in a Murine Model. Clin Exp Allergy. 2013;43(6):672–83.
15. Karin Hufnagl • Erika Jensen-Jarolim. Vitamin A and D in allergy: from experimental animal models and cellular studies to human disease. Allergo J Int. 2018;27(3):72–8
16. Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015;7(4):3011–21.
17. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effectsof 1,25-dihydroxyvitaminD3onhuman Bcelldifferentiation. J Immunol. 2007;179(3):1634–47.
18. Mak G, Hanania NA: Vitamin D and asthma. CurrOpinPulm Med. 2011;17(1):1–5.
19. Chambers ES, Hawrylowicz CM: The impact of vitamin D on regulatory T cells. Curr Allergy Asthma Rep. 2011;11(1):29–36.
20. Brehm JM, Schuemann B, Fuhlbrigge AL, et al.: Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010;126(1):52–8.
21. Ali N S, Nanji K. A Review on the Role of Vitamin D in Asthma. Cureus. 2017;9(5):e1288.
22. Hollams EM, Hart PH, Holt BJ, et al.: Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011;38(6):1320–7
23. Freishtat RJ, Iqbal SF, Pillai DK, et al.: High prevalence of vitamin D deficiency among innercity African American youth with asthma in Washington, DC. J Pediatr. 2010;156(6):948–52.
24. Chinellato I, Piazza M, Sandri M, et al.: Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr. 2011;158(3):437–41.
25. Devereux G, Wilson A, Avenell A, et al.: A case-control study of vitamin D status and asthma in adults. Allergy. 2014;65(5):666–7
26. Camargo CA, Ingham T, Wickens K, et al.: Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127(1):180–7.
27. FemkeBaeke, Tatiana Takiishi, Hannelie Korf, Conny Gysemans, Chantal Mathieu. Vitamin D: modulator of the immune system. CurrOpinPharmacol; 2010;10(4):482-96.
28. Shahin MYA, El-lawah AA, Amin A, et al.: Study of serum vitamin D level in adult patients with bronchial asthma. Egypt J Chest Dis Tuberc. 2017;66(1):5-9.
29. Kho, Alvin T, Sunita Sharma, WeiliangQiu, Roger Gaedigk, Barbara Klanderman, SiminNiu, Chris Anderson, James S Leeder, Scott T Weiss, and Kelan G Tantisira. Vitamin D related genes in lung development and asthma pathogenesis. BMC Med Genomics. 2013;6(1):47.
30. Marin L, Dufour ME, Nguyen TM, Tordet C, Garabedian M. Maturational changes induced by 1 alpha,25-dihydroxyvitamin D3 in type II cells from fetal rat lung explants. Am J Physiol. 1993; 265(1 pt 1):L45–52.
31. Xystrakis E, Kusumakar S, Boswell S, Peek E, Urry Z, Richards DF, Adikibi T, Pridgeon C, Dallman M, Loke TK, Robinson DS, Barrat FJ, O’Garra A, Lavender P, Lee TH, Corrigan C, Hawrylowicz CM. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest. 2006;116(1):146–55.
32. Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127(5):1294–6.
33. Li F, Peng M, Jiang L, Sun Q, Zhang K, Lian F, Litonjua AA, Gao J, Gao X. Vitamin D deficiency is associated with decreased lung function in Chinese adults with asthma. Respiration. 2011; 81(6):469–75.
34. Bosse Y, Maghni K, Hudson TJ. 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes. PhysiolGenomics. 2007; 29(2):161–8.
35. Wang Z, Zhang H, Sun X, Ren L. The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-beta/Smad signaling and activation of theNrf2/HO-1 pathway. Mol Med Rep. 2016;14(3):2389–96.
36. David A Jolliffe, Lauren Greenberg, Richard L Hooper, Christopher J Griffiths, Carlos A Camargo Jr, Conor P Kerley, Megan E Jensen, David Mauger, Iwona Stelmach, Mitsuyoshi Urashima, Adrian R Martineau. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet Respir Med. 2017;5(11):881–90
37. Liu ZQ, Li XX, Qiu SQ, Yu Y, Li MG, Yang LT, et al. Vitamin D contributes to mast cell stabilization. Allergy. 2017;72(8):1184–92.
| Files | ||
| Issue | Vol 20 No 5 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i5.7399 | |
| Keywords | ||
| Asthma Allergy and immunology Vitamin D | ||
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How to Cite
1.
Feng L, Meng T, Qi Y, Athari SS, Chen X. Study Effect of Vitamin D on the Immunopathology Responses of the Bronchi in Murine Model of Asthma. Iran J Allergy Asthma Immunol. 2021;20(5):509-519.
