, Volume 34, Issue 4, pp 238-246
Date: 23 Jul 2010

Suppressive Effects of Procaterol on Expression of IP-10/CXCL 10 and RANTES/CCL 5 by Bronchial Epithelial Cells

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Abstract

As indicated in the Global Initiative for Asthma guidelines, short-acting β2-adrenoreceptor agonists (SABAs) are important relievers in asthma exacerbation. Interferon γ-inducible protein (IP)-10/CXCL 10 is a T-helper type 1 (Th1) cell-related chemokine which is important in the recruitment of Th1 cells involved in host immune defense against intracellular pathogens such as viral infection. Regulated on activation, normal T expressed and secreted (RANTES)/CCL 5 is a chemokine which plays a role in attractant of eosinophils, mast cells, and basophils toward the site of allergic inflammation. Bronchial epithelial cells are first-line barriers against pathogen invasion. However, whether SABAs have regulatory effects on the expression of IP-10 and RANTES in bronchial epithelial cells is unknown. BEAS-2B cells, the human bronchial epithelial cell lines, were pretreated with procaterol (one of the SABAs) or dibutyryl-cAMP (a cyclic AMP analog) at different doses for 1 h and then stimulated with poly I:C (10 μg/mL). Supernatants were collected 12 and 24 h after poly I:C stimulation to determine the concentrations of IP-10 and RANTES by ELISA. In some cases, the cells were pretreated with selective β2-adrenoreceptor antagonist, ICI-118551, 30 min before procaterol treatment. To investigate the intracellular signaling, the cells were pretreated with mitogen-activated protein kinase (MAPK) inhibitors and a NF-κB inhibitor 30 min before procaterol treatment. Western blot was also used to explore the intracellular signaling. Procaterol significantly suppressed poly I:C-induced IP-10 and RANTES in BEAS-2B cells in a dose-dependent manner. ICI-118551, a selective β2-adrenoreceptor antagonist, could significantly reverse the suppressive effects. Dibutyryl-cAMP could confer the similar effects of procaterol on poly I:C-induced IP-10 and RANTES expression. Data of Western blot revealed that poly I:C-induced p-ERK, p-JNK, and pp38 expression, but not pp65, were suppressed by procaterol. SABAs could suppress poly I:C-induced IP-10 and RANTES expression in bronchial epithelial cells, at least in part, via β2-adrenoreceptor-cAMP and MAPK-ERK, JNK, and p38 pathways.