Vitamin E Prevents NRF2 Suppression by Allergens in Asthmatic Alveolar Macrophages in Vivo

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2011 May 25

PMID 21605660

Citations 24

Authors

Ryszard Dworski

Wei Han

Timothy S Blackwell

Aimee Hoskins

Michael L Freeman

Affiliations

Soon will be listed here.

Abstract

Asthma is a chronic inflammatory airway disease associated with increased generation of reactive oxidant species and disturbed antioxidant defenses. NRF2 is the master transcription factor that regulates the expression of Phase II antioxidant and detoxifying enzymes. Disruption of NRF2 augments oxidative stress and inflammation in a mouse model of asthma, suggesting a protective role for NRF2 in the lungs in vivo. Yet, little is known about the regulation and function of NRF2 in human asthmatics. Using segmental allergen challenge, a well-established experimental model of IgE-mediated asthma exacerbation in human atopic asthmatics, we investigated the effects of a specific allergen and the modulatory role of vitamin E on NRF2 and a NRF2-target gene, superoxide dismutase, in alveolar macrophages recovered from the airways at 24h after allergen instillation in vivo. Allergen-provoked airway inflammation in sensitive asthmatics caused a profound inhibition of macrophage NRF2 activity and superoxide dismutase, rendering them incapable of responding to the NRF2 inducers. Prolonged treatment with high doses of the antioxidant vitamin E lessened this allergen-induced drop in alveolar macrophage NRF2. These results are the first to demonstrate that NRF2 expression in human asthmatics is compromised upon allergen challenge but can be rescued by vitamin E in vivo.

Citing Articles

Dietary supplementations to mitigate the cardiopulmonary effects of air pollution toxicity: A systematic review of clinical trials.

Ilaghi M, Kafi F, Shafiei M, Zangiabadian M, Nasiri M PLoS One. 2024; 19(6):e0304402.

PMID: 38870164 PMC: 11175466. DOI: 10.1371/journal.pone.0304402.

Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma.

Britt Jr R, Ruwanpathirana A, Ford M, Lewis B Int J Mol Sci. 2023; 24(13).

PMID: 37445635 PMC: 10341920. DOI: 10.3390/ijms241310451.

Protective effects of inhaled antioxidants against air pollution-induced pathological responses.

Schichlein K, Smith G, Jaspers I Respir Res. 2023; 24(1):187.

PMID: 37443038 PMC: 10339523. DOI: 10.1186/s12931-023-02490-7.

The Role of Vitamins in the Pathogenesis of Asthma.

Zajac D, Wojciechowski P Int J Mol Sci. 2023; 24(10).

PMID: 37239921 PMC: 10218465. DOI: 10.3390/ijms24108574.

Clinically proven natural products, vitamins and mineral in boosting up immunity: A comprehensive review.

Al Mahmud A, Siddiqui S, Karim M, Al-Mamun M, Akhter S, Sohel M Heliyon. 2023; 9(4):e15292.

PMID: 37089292 PMC: 10079597. DOI: 10.1016/j.heliyon.2023.e15292.

References

Devereux G, Turner S, Craig L, McNeill G, Martindale S, Harbour P . Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J Respir Crit Care Med. 2006; 174(5):499-507. DOI: 10.1164/rccm.200512-1946OC. View

Eder W, Ege M, von Mutius E . The asthma epidemic. N Engl J Med. 2006; 355(21):2226-35. DOI: 10.1056/NEJMra054308. View

Bernstein I, Storms W . Practice parameters for allergy diagnostic testing. Joint Task Force on Practice Parameters for the Diagnosis and Treatment of Asthma. The American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1995; 75(6 Pt 2):543-625. View

Zhu H, Jia Z, Zhang L, Yamamoto M, Misra H, Trush M . Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress. Exp Biol Med (Maywood). 2008; 233(4):463-74. DOI: 10.3181/0711-RM-304. View

Wood L, Gibson P . Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma. Br J Nutr. 2009; 103(5):735-41. DOI: 10.1017/S0007114509992376. View

MacNee W . Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005; 2(1):50-60. DOI: 10.1513/pats.200411-056SF. View

Kensler T, Wakabayashi N, Biswal S . Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2006; 47:89-116. DOI: 10.1146/annurev.pharmtox.46.120604.141046. View

Rangasamy T, Guo J, Mitzner W, Roman J, Singh A, Fryer A . Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J Exp Med. 2005; 202(1):47-59. PMC: 2212893. DOI: 10.1084/jem.20050538. View

Roberts 2nd L, Oates J, Linton M, Fazio S, Meador B, Gross M . The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radic Biol Med. 2007; 43(10):1388-93. PMC: 2072864. DOI: 10.1016/j.freeradbiomed.2007.06.019. View

10.

Lang J, Gohil K, Packer L . Simultaneous determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions. Anal Biochem. 1986; 157(1):106-16. DOI: 10.1016/0003-2697(86)90203-4. View

11.

Goven D, Boutten A, Lecon-Malas V, Boczkowski J, Bonay M . Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2 and Bach1 expression in human macrophages: roles of the MAP kinases ERK(1/2) and JNK. FEBS Lett. 2009; 583(21):3508-18. DOI: 10.1016/j.febslet.2009.10.010. View

12.

Romieu I, Sienra-Monge J, Ramirez-Aguilar M, Maria Tellez-Rojo M, Moreno-Macias H, Reyes-Ruiz N . Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med. 2002; 166(5):703-9. DOI: 10.1164/rccm.2112074. View

13.

Schneider C . Chemistry and biology of vitamin E. Mol Nutr Food Res. 2004; 49(1):7-30. DOI: 10.1002/mnfr.200400049. View

14.

Busse W, Wanner A, Adams K, Reynolds H, Castro M, Chowdhury B . Investigative bronchoprovocation and bronchoscopy in airway diseases. Am J Respir Crit Care Med. 2005; 172(7):807-16. PMC: 2718402. DOI: 10.1164/rccm.200407-966WS. View

15.

Rankin J, Hitchcock M, Merrill W, Bach M, Brashler J, Askenase P . IgE-dependent release of leukotriene C4 from alveolar macrophages. Nature. 1982; 297(5864):329-31. DOI: 10.1038/297329a0. View

16.

Crapo R, Casaburi R, Coates A, Enright P, Hankinson J, Irvin C . Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000; 161(1):309-29. DOI: 10.1164/ajrccm.161.1.ats11-99. View

17.

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C . α-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010; 21(12):1222-31. DOI: 10.1016/j.jnutbio.2009.10.010. View

18.

Cockcroft D, Davis B, Boulet L, Deschesnes F, Gauvreau G, OByrne P . The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen. Allergy. 2004; 60(1):56-9. DOI: 10.1111/j.1398-9995.2004.00612.x. View

19.

Li N, Alam J, Venkatesan M, Eiguren-Fernandez A, Schmitz D, Di Stefano E . Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. J Immunol. 2004; 173(5):3467-81. DOI: 10.4049/jimmunol.173.5.3467. View

20.

Weiss K, Sullivan S . The health economics of asthma and rhinitis. I. Assessing the economic impact. J Allergy Clin Immunol. 2001; 107(1):3-8. DOI: 10.1067/mai.2001.112262. View