title: Pranlukast, a cysteinyl leukotriene type 1 receptor antagonist, attenuates the progression but not the onset of silica-induced pulmonary fibrosis in mice.
abstract: BACKGROUND
  Although cysteinyl leukotrienes (CysLTs) have been implicated in the etiology of acute inflammatory diseases, recent studies have suggested that they also directly stimulate fibroblasts. However, their precise role in the pathogenesis of pulmonary fibrosis is unclear.
  
  
  METHODS
  In this study, we evaluated the effect of both short- and long-term treatment with pranlukast, a CysLT type 1 (CysLT(1)) receptor antagonist, on silica-induced pulmonary fibrosis in mice, which is characterized by persistent progression of fibrosis in the chronic phase. Pranlukast (30 mg/kg/day) was administered orally to mice for 2 or 10 weeks after intratracheal silica instillation.
  
  
  RESULTS
  Pranlukast treatment for 10 weeks significantly attenuated the progression of pulmonary fibrosis, and decreased the content of CysLTs and LTB(4), which were markedly increased in the bronchoalveolar lavage fluid (BALF) and lung tissues of silica-instilled mice in the chronic phase. However, pranlukast treatment for 2 weeks neither affected the acute inflammatory response induced by silica instillation nor inhibited the onset of fibrosis. The expression of TGF-β1 and TNF-α was not affected by pranlukast treatment for either 2 or 10 weeks.
  
  
  CONCLUSIONS
  Pranlukast attenuates the progression of pulmonary fibrosis in the chronic phase but has no effect on the acute inflammatory response or on the onset of pulmonary fibrosis. The antifibrotic effect of pranlukast may be exhibited by antagonizing the direct profibrotic effect of CysLTs, without affecting the expression of other profibrotic cytokines such as TGF-β1 and TNF-α, and also by decreasing the production of CysLTs and LTB(4).
authors.affiliation: Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
authors.forename: Chiko
authors.initials: C
authors.lastname: Shimbori
authors.forename: Naotaka
authors.initials: N
authors.lastname: Shiota
authors.forename: Hideki
authors.initials: H
authors.lastname: Okunishi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D012822:Silicon Dioxide / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D002867:Chromones; D016207:Cytokines; D020024:Leukotriene Antagonists; D012822:Silicon Dioxide; D006909:Hydroxyproline; C047681:pranlukast