Format

Send to

Choose Destination
J Immunol. 2015 Jul 15;195(2):437-44. doi: 10.4049/jimmunol.1500362. Epub 2015 Jun 3.

Vitamin E Isoform γ-Tocotrienol Downregulates House Dust Mite-Induced Asthma.

Author information

1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228; Immunology Program, Life Science Institute, National University of Singapore, Singapore 117456;
2
Saw Swee Hock School of Public Health, National University Health System, Singapore 117597; Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore 117543;
3
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228;
4
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228; Immunology Program, Life Science Institute, National University of Singapore, Singapore 117456; Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore 117543;
5
Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore 308433;
6
Davos Life Science Private Limited, Singapore 637795; and.
7
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228; Defence Medical and Environmental Research Institute, Defence Science Organisation National Laboratories, Singapore 117510.
8
Saw Swee Hock School of Public Health, National University Health System, Singapore 117597;
9
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228; Immunology Program, Life Science Institute, National University of Singapore, Singapore 117456; phcwongf@nus.edu.sg.

Abstract

Inflammation and oxidative damage contribute to the pathogenesis of asthma. Although corticosteroid is the first-line treatment for asthma, a subset of patients is steroid resistant, and chronic steroid use causes side effects. Because vitamin E isoform γ-tocotrienol possesses both antioxidative and anti-inflammatory properties, we sought to determine protective effects of γ-tocotrienol in a house dust mite (HDM) experimental asthma model. BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts, oxidative damage biomarkers, and cytokine levels. Lungs were examined for cell infiltration and mucus hypersecretion, as well as the expression of antioxidants and proinflammatory biomarkers. Sera were assayed for IgE and γ-tocotrienol levels. Airway hyperresponsiveness in response to methacholine was measured. γ-Tocotrienol displayed better free radical-neutralizing activity in vitro and inhibition of BAL fluid total, eosinophil, and neutrophil counts in HDM mouse asthma in vivo, as compared with other vitamin E isoforms, including α-tocopherol. Besides, γ-tocotrienol abated HDM-induced elevation of BAL fluid cytokine and chemokine levels, total reactive oxygen species and oxidative damage biomarker levels, and of serum IgE levels, but it promoted lung-endogenous antioxidant activities. Mechanistically, γ-tocotrienol was found to block nuclear NF-κB level and enhance nuclear Nrf2 levels in lung lysates to greater extents than did α-tocopherol and prednisolone. More importantly, γ-tocotrienol markedly suppressed methacholine-induced airway hyperresponsiveness in experimental asthma. To our knowledge, we have shown for the first time the protective actions of vitamin E isoform γ-tocotrienol in allergic asthma.

PMID:
26041537
DOI:
10.4049/jimmunol.1500362
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center