title: Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells.
abstract: OBJECTIVE
  The alveolar epithelial cell type II (AEC-II) is itself able to amplify lung inflammation by producing inflammatory cytokines and chemokines, leading to the activation and recruitment of phagocytes. Sivelestat, a new neutrophil elastase inhibitor, has been shown to attenuate acute lung injury in animal experiments. In the current study, we assessed the effects of sivelestat on the production of chemokines from cultured A549 cells, a human AEC-II-like cell line.
  
  
  METHODS
  A549 cells were stimulated with endotoxin or tumor necrosis factor-alpha in the presence of sivelestat (1-100 microg x ml(-1)). Culture supernatant levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1 mRNAs in stimulated A549 cells in the presence of sivelestat (100 microg x ml(-1)) was quantified by real-time polymerase chain reaction.
  
  
  RESULTS
  Sivelestat, at 100 microg x ml(-1) reduced the accumulation of IL-8 and MCP-1 in the culture medium. The high dose of sivelestat significantly inhibited the expression of IL-8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not significantly.
  
  
  CONCLUSIONS
  These data suggest that a high dose of sivelestat regulates the production of IL-8 and MCP-1 in AEC-II.
authors.affiliation: Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe 650-0017, Japan.
authors.forename: Takuyo
authors.initials: T
authors.lastname: Misumi
authors.forename: Takanori
authors.initials: T
authors.lastname: Tanaka
authors.forename: Katsuya
authors.initials: K
authors.lastname: Mikawa
authors.forename: Kahoru
authors.initials: K
authors.lastname: Nishina
authors.forename: Osamu
authors.initials: O
authors.lastname: Morikawa
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Obara
mesh_terms: D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D018932:Chemokine CCL2; D004731:Endotoxins; D016209:Interleukin-8; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C069195:sivelestat; D005998:Glycine