Supplementation with γ-tocopherol attenuates endotoxin-induced airway neutrophil and mucous cell responses in rats
| Autor: | Daven N. Jackson-Humbles, James G. Wagner, Qing Jiang, David B. Peden, Neil P. Birmingham, Jack R. Harkema |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Neutrophils medicine.medical_treatment gamma-Tocopherol Mucous membrane of nose Respiratory Mucosa Lung injury Biochemistry Article chemistry.chemical_compound Physiology (medical) Medicine Animals medicine.diagnostic_test business.industry Vitamin E Mucin Mucins Lung Injury respiratory system Rats Nasal Mucosa Bronchoalveolar lavage chemistry Gene Expression Regulation Immunology Dietary Supplements business Bronchoalveolar Lavage Fluid Prostaglandin E |
| Zdroj: | Free radical biologymedicine. 68 |
| ISSN: | 1873-4596 |
| Popis: | Neutrophil-mediated tissue injury is a shared pathogenesis of both chronic pulmonary diseases and acute responses to pathogens, allergens, and airborne pollutants. Interventions to minimize toxic effects of neutrophil-derived oxidants and proteases are usually limited to corticosteroids, which can have adverse side effects. We used a rodent model of endotoxin-induced lung injury to test the hypothesis that the dietary supplement γ-tocopherol (γT), a natural form of vitamin E with antioxidant and novel anti-inflammatory properties, will protect from adverse nasal and pulmonary inflammatory responses induced by endotoxin (lipopolysaccharide; LPS). Male Fisher F344 rats were intranasally (i.n.) instilled with LPS for 2 consecutive days. Beginning 2 days before i.n. LPS, the rats were gavaged daily with 30 mg/kg γT. Twenty-four hours after the last i.n. LPS, bronchoalveolar lavage fluid (BALF) was collected, and pulmonary and nasal tissues were analyzed for gene expression and morphometric analyses of neutrophils and intraepithelial mucosubstances (IM). LPS caused increased BALF total cells (70% increase), neutrophils (300%), protein (35%), PGE2 (500%), and secreted mucins (75%). Robust increases in neutrophils and IM were detected in conducting airways. Pulmonary expression of MUC5AC, MIP-2, CINC-1, and MCP-1 was elevated three- to eightfold by LPS. Treatment with γT inhibited LPS-induced increases in BALF total cells, neutrophils, protein, PGE2, and secreted mucins, as well as IM and tissue neutrophil influx. Furthermore γT induced the expression of the regulatory cytokines IL-10 and IFN-γ while decreasing MUC5AC, MIP-2, CINC-1, and MCP-1. These data demonstrate novel therapeutic effects of the dietary vitamin E γT promoting anti-inflammatory pathways to protect from neutrophil-mediated lung injury. |
| Databáze: | OpenAIRE |
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