Basic research on virus-induced asthma exacerbation: Inhibition of inflammatory chemokine expression by fluticasone propionate

Satoshi Matsukura*, Masatsugu Kurokawa, Tetsuya Homma, Shin Watanabe, Shintaro Suzuki, Koushi Ieki, Hiroko Takeuchi, Kyoko Notomi, Robert P. Schleimer, Mio Kawaguchi, Fumio Kokubu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Viral infection can exacerbate asthma by inducing the accumulation of inflammatory cells in the airway. We have previously reported that double-stranded RNA (dsRNA), a viral product and ligand of the Toll-like receptor-3 (TLR3), activates the transcription factors NF-κB and IRF-3 and upregulates the expression of inflammatory chemokines in airway epithelial cells. Here, we examined the effects of the glucocorticoid fluticasone propionate (FP) on the expression of the inflammatory chemokines CCL5, CXCL8 and CXCL10. Methods: The airway epithelial cell line BEAS-2B was used for this study. Expression of CCL5, CXCL8 and CXCL10 mRNA and protein was quantified by real-time PCR and ELISA assay, respectively. To examine the association of FP with the physiology of chemokine production, we included several methods. Nuclear translocation of transcription factors was determined by performing Western blot analysis. Histone deacetylase (HDAC) activity in nuclear extracts was measured using a colorimetric assay. Stability of the chemokine mRNAs was examined in cells incubated with actinomycin D. The activities of the CCL5 promoter and the transcription factors NF-κB and IRF-3 were assessed using luciferase reporter assays. Results: Treatment of BEAS-2B cells with FP significantly and dose-dependently (10-9 to 10-6M) inhibited dsRNA-induced expression of CCL5, CXCL8 and CXCL10 protein and mRNA, but did not affect mRNA stability. FP also significantly inhibited dsRNA-stimulated CCL5 promoter activity. However, FP had no effect on the activity of HDAC or the nuclear translocation of NF-κB and IRF-3. Conclusions: FP inhibits the dsRNA-stimulated expression of inflammatory chemokines in airway epithelial cells. FP may act by inhibiting chemokine transcription through an as yet unidentified mechanism.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalInternational archives of allergy and immunology
Volume161
DOIs
StatePublished - Apr 12 2013

Keywords

  • Airway epithelial cells
  • Glucocorticoids
  • Inflammatory chemokines
  • Virus-induced asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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