title: Supplementation with γ-tocopherol attenuates endotoxin-induced airway neutrophil and mucous cell responses in rats.
abstract: 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 30mg/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.
authors: Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA. Electronic address: wagnerja@msu.edu.
authors: James G
authors: JG
authors: Wagner
authors: Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA.
authors: Neil P
authors: NP
authors: Birmingham
authors: Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
authors: Daven
authors: D
authors: Jackson-Humbles
authors: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors: Qing
authors: Q
authors: Jiang
authors: Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
authors: Jack R
authors: JR
authors: Harkema
authors: Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: David B
authors: DB
authors: Peden
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D024504:gamma-Tocopherol / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D009077:Mucins; D024504:gamma-Tocopherol
keywords: Endotoxin; Free radicals; Intraepithelial mucosubstances; Neutrophil; Prostaglandin E(2); γ-Tocopherol