Effect of obesity on pulmonary inflammation induced by acute ozone exposure: role of interleukin-6

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 294; no. 5; pp. L1013 - L1020
• Main Authors: Lang, Jason E, Williams, Erin S, Mizgerd, Joseph P, Shore, Stephanie A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.05.2008
• Subjects: Acute Disease; Air pollution; Animals; Antibodies - pharmacology; Body Weight; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Cytokines; Female; Genotypes; Inflammatory diseases; Interleukin-6 - immunology; Interleukin-6 - metabolism; Leukemia; Male; Mice; Mice, Obese; Neutralization; Neutrophils - immunology; Neutrophils - metabolism; Obesity; Obesity - complications; Obesity - immunology; Ozone; Ozone - toxicity; Pneumonia - chemically induced; Pneumonia - complications; Pneumonia - immunology; Respiratory diseases; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00122.2007

Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts Submitted 28 March 2007 ; accepted in final form 17 March 2008 To determine the role of interleukin (IL)-6 in the increased ozone (O 3 )-induced inflammation and injury observed in obese vs. lean mice, lean wild-type and leptin-deficient obese ( ob/ob ) mice were injected with anti-IL-6 antibody (Ab) or isotype control Ab 24 h before exposure to either O 3 (2 ppm for 3 h) or room air. Four or 24 h after O 3 exposure, bronchoalveolar lavage (BAL) was performed, and the lungs were harvested for Western blotting. Anti-IL-6 Ab caused substantial reductions in O 3 -induced increases in BAL IL-6 in mice of both genotypes. Four hours following O 3 , ob/ob mice had increased BAL neutrophils compared with controls, and anti-IL-6-Ab virtually abolished this difference. At 24 h, O 3 -induced increases in BAL protein and BAL serum albumin were augmented in ob/ob vs. wild-type mice, and anti-IL-6 Ab ablated these obesity-related differences in epithelial barrier injury. O 3 increased tyrosine phosphorylation of STAT-3 and STAT-1. There was no effect of obesity on STAT-3 phosphorylation, whereas obesity decreased STAT-1 expression, resulting in reduced STAT-1 phosphorylation. IL-6 neutralization did not alter STAT-3 or STAT-1 phosphorylation in ob/ob or wild-type mice. O 3 increased BAL leukemia inhibitory factor (LIF) to a greater extent in obese than in lean mice, and LIF may account for effects on STAT phosphorylation. Our results suggest that IL-6 plays a complex role in pulmonary responses to O 3 , a role that differs between wild-type and ob/ob mice. Moreover, obesity-related differences in activation of STAT proteins may contribute to some of the differences in the response of obese vs. lean mice. neutrophil; airway; chemokine; STAT-3; STAT-1; leukemia inhibitory factor Address for reprint requests and other correspondence: S. A. Shore, Molecular and Integrative Physiological Sciences Program, Dept. of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115-6021 (e-mail: sshore{at}hsph.harvard.edu )