title: Corticosteroids plus long-acting β2-agonists prevent double-stranded RNA-induced upregulation of B7-H1 on airway epithelium.
abstract: BACKGROUND
  Airway viral infections provoke exacerbations of asthma and chronic obstructive pulmonary disease. B7-H1 is a costimulatory molecule that is implicated in an escape mechanism of viruses from host immune systems. This escape may be associated with the persistence of viral infection and lead to exacerbation of underlying diseases. We have shown that an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1 on airway epithelial cells, an effect which was corticosteroid-resistant. We investigated the effects of corticosteroids plus long-acting β(2)-agonists (LABAs; fluticasone/salmeterol or budesonide/formoterol) on the expression of B7-H1.
  
  
  METHODS
  BEAS-2B cells and primary airway epithelial cells were stimulated with poly IC or respiratory syncytial virus. The expression of B7-H1 was assessed by flow cytometry.
  
  
  RESULTS
  Poly IC upregulated the expression of B7-H1, which was suppressed by high-concentration corticosteroids but not by LABAs. The upregulation was suppressed by very low-concentration corticosteroids when used in combination with LABAs. Their combination also suppressed the virus-induced upregulation of B7-H1. Poly IC stimulation induced the nuclear translocation of nuclear factor ĸB (NF-ĸB). Inhibitors of NF-ĸB activation prevented the poly IC-induced upregulation of B7-H1. Low-concentration corticosteroids in combination with LABAs enhanced the de novo induction of IĸBα, the endogenous inhibitor of NF-ĸB activation.
  
  
  CONCLUSIONS
  Fluticasone/salmeterol or budesonide/formoterol attenuate the virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-ĸB activation.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kan-O
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Y
authors.initials: Y
authors.lastname: Asai
authors.forename: W
authors.initials: W
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: J
authors.initials: J
authors.lastname: Araya
authors.forename: K
authors.initials: K
authors.lastname: Kuwano
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000378:metabolism*; D019819:Budesonide / Q000494:pharmacology; D002460:Cell Line; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology; D000068297:Fluticasone-Salmeterol Drug Combination; D000068759:Formoterol Fumarate; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity; D015854:Up-Regulation
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D004338:Drug Combinations; D004983:Ethanolamines; D000068297:Fluticasone-Salmeterol Drug Combination; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D019819:Budesonide; D011070:Poly I-C; D000420:Albuterol; D000068759:Formoterol Fumarate