Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 294; no. 6; pp. L1174 - L1186
• Main Authors: Yao, Hongwei, Edirisinghe, Indika, Rajendrasozhan, Saravanan, Yang, Se-Ran, Caito, Samuel, Adenuga, David, Rahman, Irfan
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2008
• Subjects: Aldehydes - metabolism; Animals; Bronchoalveolar Lavage Fluid - cytology; Cells; Chemokines - biosynthesis; Chronic obstructive pulmonary disease; Cytokines - biosynthesis; Glutamate-Cysteine Ligase - metabolism; Glutathione - metabolism; Histone Deacetylase 2; Histone Deacetylases - metabolism; Lipid Peroxidation; Lung - metabolism; Lungs; Male; Malondialdehyde - metabolism; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Molecules; NF-kappa B - metabolism; Oxidation; p38 Mitogen-Activated Protein Kinases - metabolism; Pneumonia - etiology; Pneumonia - physiopathology; Repressor Proteins - metabolism; Rodents; Smoking - adverse effects; Species Specificity; Studies
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00439.2007

Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York Submitted 22 October 2007 ; accepted in final form 25 March 2008 A variety of mouse models have been used to study the pathogenesis of pulmonary emphysema/chronic obstructive pulmonary disease. The effect of cigarette smoke (CS) is believed to be strain dependent, because certain mouse strains are more susceptible or resistant to development of emphysema. However, the molecular basis of susceptibility of mouse strains to effects of CS is not known. We investigated the effect of CS on lungs of most of the commonly used mouse strains to study the molecular mechanism of susceptibility to effects of CS. C57BL/6J, A/J, AKR/J, CD-1, and 129SvJ mice were exposed to CS for 3 consecutive days, and various parameters of inflammatory and oxidative responses were assessed in lungs of these mice. We found that the C57BL/6J strain was highly susceptible, the A/J, AKR/J, and CD-1 strains were moderately susceptible, and the 129SvJ strain was resistant to lung inflammatory and oxidant responses to CS exposure. The mouse strain that was more susceptible to effects of CS showed augmented lung inflammatory cell influx, activation of NF- B and p38 MAPK, and increased levels of matrix metalloproteinase-9 and NF- B-dependent proinflammatory cytokines compared with resistant mouse strains. Similarly, decreased levels of glutathione were associated with increased levels of lipid peroxidation products in susceptible mouse strains compared with resistant strains. Hence, we identified the susceptible and resistant mouse strains on the basis of the pattern of inflammatory and oxidant responses. Identification of sensitive and resistant mouse strains could be useful for studying the molecular mechanisms of effects of CS on inflammation and pharmacological interventional studies in CS-exposure mouse models. nuclear factor- B; histone deacetylase-2; p38 MAPK; lipid peroxides; glutathione; chronic obstructive pulmonary disease Address for reprint requests and other correspondence: I. Rahman, Dept. of Environmental Medicine, Lung Biology and Disease Program, Univ. of Rochester Medical Center, 601 Elmwood Ave., Box 850, Rochester, NY 14642 (e-mail: irfan_rahman{at}urmc.rochester.edu )