title: Sevoflurane suppresses tumour necrosis factor-α-induced inflammatory responses in small airway epithelial cells after anoxia/reoxygenation.
abstract: BACKGROUND
  Lung ischaemia-reperfusion (I/R) injury is correlated with poor clinical outcome. The inflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) are produced by pulmonary epithelial cells during lung transplantation and are considered to be involved in I/R injury. The volatile anaesthetic sevoflurane has been shown to exert a protective effect on I/R injury in various organs. We investigated the effect of sevoflurane on the inflammatory functions of pulmonary epithelial cells in vitro.
  
  
  METHODS
  Human normal small airway epithelial cells (SAEC) were incubated under anoxic conditions for 24 h with or without sevoflurane and then stimulated with tumour necrosis factor (TNF)-α under hyperoxic conditions for 5 h with or without sevoflurane. After incubation, IL-6, IL-8, and MCP-1 mRNA expression was analysed by quantitative real-time RT-PCR. The production of IL-6, IL-8, and MCP-1 was assayed by enzyme-linked immunosorbent assay, the effects of sevoflurane on inflammatory gene expression were examined by DNA microarray analysis, and the effects of sevoflurane on NF-κB-mediated inflammatory cytokine production were examined by immunoblotting.
  
  
  RESULTS
  Sevoflurane suppressed TNF-α-induced IL-6, IL-8, and MCP-1 gene expression and the production of IL-6 and IL-8 in SAEC under anoxia/reoxygenation conditions. DNA microarray analysis indicated that sevoflurane modulated NF-κB-related gene expression. Sevoflurane significantly inhibited TNF-α-induced translocation of p65 NF-κB into the nucleus. Sevoflurane enhanced TNF-α-induced gene expression of inhibitor κB (IκB) but not of NF-κB.
  
  
  CONCLUSIONS
  Sevoflurane suppressed the NF-κB-mediated production of pulmonary epithelial cell-derived inflammatory cytokines, including IL-6 and IL-8, which are capable of causing I/R injury.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: C
authors.initials: C
authors.lastname: Iwahara
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: T
authors.initials: T
authors.lastname: Matsukawa
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kamiyama
authors.forename: E
authors.initials: E
authors.lastname: Inada
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008738:Methyl Ethers / Q000494:pharmacology*; D046228:Microarray Analysis; D008928:Mitochondria / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D000077149:Sevoflurane; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018685:Anesthetics, Inhalation; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D018076:DNA, Complementary; D015850:Interleukin-6; D016209:Interleukin-8; D008738:Methyl Ethers; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000077149:Sevoflurane