Vitamin E Isoform γ-Tocotrienol Downregulates House Dust Mite−Induced Asthma
The Journal of Immunology, 2015, 195: 000–000.
Published June 3, 2015
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 g-tocotrienol possesses both antioxidative and anti-inﬂammatory properties, we sought to determine protective effects of g-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 bio-markers. Sera were assayed for IgE and g-tocotrienol levels. Airway hyperresponsiveness in response to methacholine was measured. g-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 a-tocopherol. Besides, g-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. Mech-anistically, g-tocotrienol was found to block nuclear NF-kB level and enhance nuclear Nrf2 levels in lung lysates to greater extents than did a-tocopherol and prednisolone. More importantly, g-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 g-tocotrienol in allergic asthma.
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