β2-adrenoceptor agonists enhance cytokine-induced release of thymic stromal lymphopoietin by lung tissue cells

Kyoko Futamura, Kanami Orihara, Noriko Hashimoto, Hideaki Morita, Shuhei Fukuda, Hironori Sagara, Kenji Matsumoto, Yasushi Tomita, Hirohisa Saito, Akio Matsuda

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17 Citations (Scopus)

Abstract

Background: Whileβ2-adrenoceptor agonists (β2-agonists) are widely used as bronchodilators in the treatment of asthma, there has been increasing concern that regular use of β2-agonists may adversely affect the control of asthma. However, the molecular mechanisms of such undesirable effects of β2- agonists are not fully understood. In this study, we examined the effects of β2-agonists on cytokine-induced production of thymic stromal lymphopoietin (TSLP), an indispensable cytokine in the development of allergic diseases, by lung tissue cells. Methods: Normal human bronchial epithelial cells (NHBE), smooth muscle cells (BSMC) and fibroblasts (NHLF) were stimulated with the IL-4 and TNF-α cytokines, alone and in combination, and their production of TSLP was examined by ELISA. The effects of β2- agonists (salmeterol, formoterol, salbutamol), intracellular cyclic adenosine monophosphate (cAMP)-elevating agents (8-bromo-cAMP, dibutyryl cAMP, forskolin) and a corticosteroid (fluticasone) on the cytokine-induced TSLP production were examined. Results: The following results were observed in all three types of lung tissue cells tested (that is, NHBE, BSMC and NHLF). Costimulation with IL-4 and TNF-α significantly induced TSLP production, and β2- agonists further enhanced it via upregulation of intracellular cAMP. However, addition of a corticosteroid to the cytokines and β2-agonist resulted in a marked decrease in TSLP production. Conclusions: β2-Agonists significantly enhanced the cytokine-induced TSLP production by primary human lung tissue cells. This may be partly responsible for the undesirable clinical effects of continuous β2-agonist monotherapy, and combination therapy with a corticosteroid might effectively inhibit TSLP-mediated allergic inflammation.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalInternational Archives of Allergy and Immunology
Volume152
Issue number4
DOIs
Publication statusPublished - 07-2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Futamura, K., Orihara, K., Hashimoto, N., Morita, H., Fukuda, S., Sagara, H., Matsumoto, K., Tomita, Y., Saito, H., & Matsuda, A. (2010). β2-adrenoceptor agonists enhance cytokine-induced release of thymic stromal lymphopoietin by lung tissue cells. International Archives of Allergy and Immunology, 152(4), 353-361. https://doi.org/10.1159/000288288