title: p38 Mitogen-activated protein kinase accelerates emphysema in mouse model of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  There are few short-term mouse models of chronic obstructive pulmonary disease (COPD) mimicking the human disease. In addition, p38 is recently recognized as a target for the treatment of COPD. However, the precise mechanism how p38 contributes to the pathogenesis of COPD is still unknown.
  
  
  OBJECTIVE
  We attempted to create a new mouse model for COPD by intra-tracheal administration of a mixture of lipopolysaccharide (LPS) and cigarette smoke solution (CSS), and investigated the importance of the p38 mitogen-activated protein kinase (p38) pathway in the pathogenesis of COPD.
  
  
  METHODS
  Mice were administered LPS + CSS once a day on days 0-4 and 7-11. Thereafter, CSS alone was administered to mice once a day on days 14-18. On day 28, histopathological changes of the lung were evaluated, and bronchoalveolar lavage fluid (BALF) was subjected to western blot array for cytokines. Transgenic (TG) mice expressing a constitutive-active form of MKK6, a p38-specific activator in the lung, were subjected to our experimental protocol of COPD model.
  
  
  RESULTS
  LPS + CSS administration induced enlargement of alveolar air spaces and destruction of lung parenchyma. BALF analyses of the LPS + CSS group revealed an increase in expression levels of several cytokines involved in the pathogenesis of human COPD. These results suggest that our experimental protocol can induce COPD in mice. Likewise, histopathological findings of the lung and induction of cytokines in BALF from MKK6 c.a.-TG mice were more marked than those in WT mice.
  
  
  CONCLUSIONS
  In a new experimental COPD mouse model, p38 accelerates the development of emphysema.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology .
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Amano
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsunaga
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kento
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sudo
authors.forename: Sadao
authors.initials: S
authors.lastname: Kimura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Kasuya
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004646:Emphysema / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D048669:MAP Kinase Kinase 6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D062789:Tobacco Products / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse
keywords: COPD mouse model; Cigarette smoke; MKK6 c.a.; lipopolysaccharide; transgenic mouse