Procaterol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells

Mutsuo Yamaya, Hidekazu Nishimura, Yukimasa Hatachi, Motoki Yoshida, Hidenori Fujiwara, Masanori Asada, Katsutoshi Nakayama, Hiroyasu Yasuda, Xue Deng, Takahiko Sasaki, Hiroshi Kubo, Ryoichi Nagatomi

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19 Citations (Scopus)

Abstract

β2 agonists reduce the frequency of exacerbations in patients with bronchial asthma and chronic obstructive pulmonary disease caused by respiratory virus infection. β2 agonists reduce the production of pro-inflammatory cytokines. However, the inhibitory effects of β2 agonists on the infection of rhinovirus, the major cause of exacerbations, have not been well studied. To examine the effects of a β2 agonist, procaterol, on rhinovirus infection and rhinovirus infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group rhinovirus, type 14 rhinovirus. Rhinovirus infection increased viral titers and the content of pro-inflammatory cytokines, including interleukin-1β and interlukin-6, in supernatant fluids and rhinovirus RNA in the cells. Procaterol reduced rhinovirus titers and RNA, cytokine concentrations, and susceptibility to rhinovirus infection. Procaterol reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for type 14 rhinovirus, and the number of acidic endosomes in the cells from which rhinovirus RNA enters into the cytoplasm. Procaterol inhibited the activation of nuclear factor kappa-B (NF-κB) proteins including p50 and p65 in the nuclear extracts, while it increased the cytosolic amount of the inhibitory kappa B-α and intracellular cyclic AMP (cAMP) levels. A selective β2-adrenergic receptor antagonist ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] reversed the inhibitory effects of procaterol on rhinovirus titers and RNA, susceptibility to rhinovirus infection, pro-inflammatory cytokines production, ICAM-1 expression, acidic endosomes, and NF-κB. ICI 118551 also reversed the effects of procaterol on cAMP levels. Procaterol may inhibit rhinovirus infection by reducing ICAM-1 and acidic endosomes as well as modulate airway inflammation in rhinovirus infection.

Original languageEnglish
Pages (from-to)431-444
Number of pages14
JournalEuropean Journal of Pharmacology
Volume650
Issue number1
DOIs
Publication statusPublished - 2011 Jan 10

Keywords

  • Acidic endosome
  • Human tracheal epithelial cell
  • Intercellular adhesion molecule
  • Pro-inflammatory cytokine
  • Procaterol
  • Rhinovirus

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Yamaya, M., Nishimura, H., Hatachi, Y., Yoshida, M., Fujiwara, H., Asada, M., Nakayama, K., Yasuda, H., Deng, X., Sasaki, T., Kubo, H., & Nagatomi, R. (2011). Procaterol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. European Journal of Pharmacology, 650(1), 431-444. https://doi.org/10.1016/j.ejphar.2010.09.056