title: Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice.
abstract: 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-kappaB and p38 MAPK, and increased levels of matrix metalloproteinase-9 and NF-kappaB-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.
authors: Lung Biology and Disease Program, Deptartment of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 850, Rochester, New York 14642, USA.
authors: Hongwei
authors: H
authors: Yao
authors: Indika
authors: I
authors: Edirisinghe
authors: Saravanan
authors: S
authors: Rajendrasozhan
authors: Se-Ran
authors: SR
authors: Yang
authors: Samuel
authors: S
authors: Caito
authors: David
authors: D
authors: Adenuga
authors: Irfan
authors: I
authors: Rahman
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D015227:Lipid Peroxidation; D008168:Lung / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000503:physiopathology*; D012097:Repressor Proteins / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013045:Species Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000447:Aldehydes; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D012097:Repressor Proteins; D008315:Malondialdehyde; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal