title: Immunohistochemical study of lung remodeling in mice exposed to cigarette smoke*.
abstract: OBJECTIVE
  Various studies of emphysema involve long-term exposure of animals to cigarette smoke, focusing on the cell type involved in the protease/antiprotease imbalance and on extracellular matrix degradation. In emphysema, increased expression of metalloproteinases is associated with cytokines, and evidence suggests that the matrix metalloproteinase-12 (MMP-12) plays an important role. Our objective was to investigate tissue inhibitor of metalloproteinase-2 (TIMP-2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) detection by immunohistochemical methods in mouse lung.
  
  
  METHODS
  Male C57BL/6 mice were exposed 3 times a day to smoke of 3 cigarettes over a period of 10, 20, 30 or 60 days in an inhalation chamber (groups CS10, CS20, CS30 and CS60, respectively). Controls were exposed to the same conditions in room air.
  
  
  RESULTS
  A progressive increase in the number of alveolar macrophages was observed in the bronchoalveolar lavage fluid of the exposed mice. The mean linear intercept, an indicator of alveolar destruction, was greater in all exposed groups when compared to control group. In the CS10, CS20 and CS30 mice, the immunohistochemical index (II) for MMP-12 increased in parallel with a decrease in II for TIMP-2 in the CS10, CS20 and CS30 mice. The II for the cytokines TNF-alpha and IL-6 was greater in all exposed groups than in the control group. Emphysema, with changes in volume density of collagen and elastic fibers, was observed in the CS60 group.
  
  
  CONCLUSIONS
  These findings suggest that cigarette smoke induces emphysema with major participation of TNF-alpha and IL-6 without participation of neutrophils.
authors.affiliation: Departamento de Histologia e Embriologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Samuel Santos
authors.initials: SS
authors.lastname: Valença
authors.forename: Luís Cristóvão
authors.initials: LC
authors.lastname: Porto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D053508:Matrix Metalloproteinase 12