β2-Adrenoceptor Agonists Enhance Cytokine-Induced Release of Thymic Stromal Lymphopoietin by Lung Tissue Cells

Background: While � 2 -adrenoceptor agonists ( � 2 -agonists) are widely used as bronchodilators in the treatment of asthma, there has been increasing concern that regular use of � 2 -agonists may adversely affect the control of asthma. However, the molecular mechanisms of such undesirable effects of � 2 -agonists are not fully understood. In this study, we examined the effects of � 2 -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- � cytokines, alone and in combination, and their production of TSLP was examined by ELISA. The effects of � 2 -agonists (salmeterol, formoterol, salbutamol), intracellular cyclic adenosine monophosphate (cAMP)-elevating agents (8bromo-cAMP, dibutyryl cAMP, forskolin) and a corticosteroid (fluticasone) on the cytokine-induced TSLP production were