title: Preventive effect of irbesartan on bleomycin-induced lung injury in mice.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia that is limited to the lung. Angiotensin receptor blockers (ARBs) and peroxisome proliferator-activated receptor (PPAR) γ ligands have anti-inflammatory and anti-fibrotic effects. We investigated the effects of irbesartan-an ARB with PPAR γ activity-on the development of bleomycin-induced pulmonary fibrosis in mice.
  
  
  METHODS
  Lung injury was induced in imprinting control region (ICR) mice by intratracheal instillation of 2mg/kg of bleomycin. The treatment group orally received 20mg/kg of irbesartan for 5 consecutive days before instillation. The mice were sacrificed and were evaluated 14 days after bleomycin instillation.
  
  
  RESULTS
  Irbesartan reduced the fluid content and hydroxyproline level in the lung and improved the pathological findings as indicated by the Ashcroft score. Total cell counts, the numbers of macrophages, neutrophils, and lymphocytes, and the levels of transforming growth factor (TGF) β1 and monocyte chemotactic protein (MCP) 1 in the bronchoalveolar lavage fluid (BALF) were decreased. Treatment with a PPARγ antagonist GW9662 reversed some of the effects of irbesartan.
  
  
  CONCLUSIONS
  The results of this study indicated that irbesartan attenuated the development of bleomycin-induced pulmonary fibrosis in mice by decreasing TGF-β1 and MCP-1 via blocking of ATI, by binding to CCR2b, and by PPARγ-mediated inhibition of inflammation.
authors.affiliation: Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shunji
authors.initials: S
authors.lastname: Tajima
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Asakawa
authors.forename: Takuro
authors.initials: T
authors.lastname: Sakagami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takada
authors.forename: Eiichi
authors.initials: E
authors.lastname: Suzuki
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects*; D018932:Chemokine CCL2 / Q000032:analysis; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy*; D000077405:Irbesartan; D008297:Male; D051379:Mice; D013777:Tetrazoles / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000903:Antibiotics, Antineoplastic; D001713:Biphenyl Compounds; D018932:Chemokine CCL2; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D000077405:Irbesartan