Corticosteroid and cytokines synergistically enhance toll-like receptor 2 expression in respiratory epithelial cells

Toshiki Homma, Atsushi Kato, Noriko Hashimoto, Jonathan Batchelor, Mamoru Yoshikawa, Shosuke Imai, Hiroshi Wakiguchi, Hirohisa Saito, Kenji Matsumoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Respiratory epithelial cells play important roles not only in host defense mechanisms, but also in inflammatory responses. Inhaled corticosteroids are widely used for the treatment of patients with inflammatory lung disorders, including asthma, chronic obstructive pulmonary disease, and sarcoidosis. Corticosteroids effectively reduce the production of inflammatory mediators, such as cytokines and chemokines. Although these molecules are also essential for host defense responses, there is no convincing evidence that inhaled corticosteroids increase susceptibility to lower respiratory tract infections. To test the involvement of Toll-like receptor (TLR) family molecules in this phenomenon, we examined the effects of various cytokines and corticosteroid on the expression of TLRs in human respiratory epithelial cells. Among the TLRs tested, TLR2 expression was significantly enhanced after stimulation with a combination of tumor necrosis factor-α and interferon-γ. Dexamethasone synergistically enhanced TLR2 expression in combination with tumor necrosis factor-α and interferon-γ in terms of both mRNA and protein levels. Furthermore, increased cell-surface TLR2 was functional, judging from the remarkable induction of interleukin-6, interleukin-8, and β-defensin-2 after stimulation with peptidoglycan. These results provide evidence for a novel function of corticosteroids in airway inflammatory disorders, and indicate that the use of inhaled corticosteroids in such disorders may have a beneficial role in host defense mechanisms.

Original languageEnglish (US)
Pages (from-to)463-469
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume31
Issue number4
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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