Infection of human respiratory submucosal glands with rhinovirus: Effects on cytokine and ICAM-1 production

Mutsuo Yamaya, Kiyohisa Sekizawa, Tomoko Suzuki, Norihiro Yamada, Masayuki Furukawa, Satoshi Ishizuka, Katsutoshi Nakayama, Masanori Terajima, Yoshio Numazaki, Hidetada Sasaki

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


To further understand the early biochemical events that occur in infected surface epithelium, we developed for the first time a model in which a respiratory submucosal gland cell population can be infected with rhinovirus (RV). Viral infection was confirmed by demonstrating with PCR that viral titers in supernatants and lysates from infected cells increased with time. Infection by RV14 upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major RV receptor, on submucosal gland cells, and it increased production of interleukin (IL)-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor in supernatants. Antibodies to ICAM-1 inhibited RV infection of submucosal gland cells and decreased the production of cytokines after RV infection. Both IL-Iα and IL-1β upregulated ICAM-1 mRNA expression and increased susceptibility to RV infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, neutralizing antibodies to IL-1α and IL-1β significantly decreased the viral titers in supernatants and ICAM- 1 mRNA expression after RV infection, but a neutralizing antibody to tumor necrosis factor-α was without effect. These findings suggest that respiratory submucosal gland cells play an important role in the initial stages of inflammation and provide useful insights into the pathogenesis of RV infection.

Original languageEnglish
Pages (from-to)L362-L371
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2 21-2
Publication statusPublished - 1999 Aug


  • Airway inflammation
  • Asthma
  • Common cold
  • Intercellular adhesion molecule-1
  • Interleukin-1
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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