Corticosteroids plus long-acting Beta2-agonists prevent double-stranded RNA-induced upregulation of B7-H1 on airway epithelium

K. Kan-O, K. Matsumoto, H. Inoue, S. Fukuyama, Y. Asai, W. Watanabe, M. Kurokawa, J. Araya, K. Kuwano, Y. Nakanishi

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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 β2-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 κB (NF-κB). Inhibitors of NF-κB activation prevented the poly IC-induced upregulation of B7-H1. Low-concentration corticosteroids in combination with LABAs enhanced the de novo induction of IκBα, the endogenous inhibitor of NF-κB activation. Conclusions: Fluticasone/salmeterol or budesonide/formoterol attenuate the virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-κB activation.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalInternational Archives of Allergy and Immunology
Volume160
Issue number1
DOIs
Publication statusPublished - Dec 1 2012

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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