title: N-acetylcysteine inhibits interleukin-17-induced interleukin-8 production from human airway smooth muscle cells: a possible role for anti-oxidative treatment in chronic lung rejection?
abstract: BACKGROUND
  Long-term survival of lung transplantation is threatened by obliterative bronchiolitis, or its clinical equivalent, bronchiolitis obliterans syndrome. With a prevalence of >50% at 5 years after transplantation, it has emerged as the most significant long-term complication. Neutrophilic inflammation and increased interleukin (IL)-8 production seem to be part of the basic pathophysiologic mechanism of chronic rejection. Recently, it has been suggested that reactive oxygen species may also play an important role in the pathogenesis because they are known to induce smooth muscle proliferation.
  
  
  METHODS
  Human airway smooth muscle cells in vitro were stimulated with IL-17 (0.1 to 10 ng/ml) or with IL-17 (10 ng/ml) and the anti-oxidative agent N-acetylcysteine (1 micromol/liter to 10 mmol/liter). Production of 8-isoprostane was measured with a commercially available enzyme immunoassay kit and production of IL-8 was measured using a standard enzyme-linked immunoassay technique.
  
  
  RESULTS
  IL-17 produced a concentration-dependent increase in 8-isoprostane with a maximum of 136.5 +/- 15.5 pg/ml with IL-17 (10 ng/ml, p < 0.001, n = 12, vs unstimulated cells). N-acetylcysteine (NAC) was able to decrease IL-17-induced 8-isoprostane production, with a maximum decrease of 59.3 +/- 9% (p < 0.001, n = 12) with 10 mmol/liter of N-acetylcysteine, which also decreased IL-17-induced IL-8 production in a concentration-dependent manner (with maximum inhibition of 86.3% when combined with NAC 10 mmol/liter as compared with IL-17 alone).
  
  
  CONCLUSIONS
  We demonstrated that human airway smooth muscle cells, when stimulated with IL-17, are able to produce 8-isoprostane, which could be inhibited by adding N-acetylcysteline, and which was also able to decrease IL-17-induced IL-8 production. The clinical significance of these in vitro findings for prevention or treatment of chronic rejection after lung transplantation remains to be investigated.
authors.affiliation: Laboratory of Pneumology, Katholieke University Leuven, Leuven, Belgium.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.forename: Maurits G
authors.initials: MG
authors.lastname: Demedts
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D028421:Isoprostanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016040:Lung Transplantation / Q000276:immunology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D020381:Interleukin-17; D016209:Interleukin-8; D028421:Isoprostanes; D017382:Reactive Oxygen Species; D000111:Acetylcysteine