Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells

To cite this article: Lam KP, Chu YT, Lee MS, Chen HN, Wang WL, Tok TS, Chin YY, Chen SC, Kuo CH, and Hung CH. Inhibitory Effects of Albuterol and Fenoterol on RANTES and IP‐10 Expression in Bronchial Epithelial Cells. Pediatric Allergy Immunology 2011; 22: 431–439. Short‐acting β2‐adrenoreceptor agonist (SABA) is the major asthma reliever as indicated in the GINA guidelines. Regulated on activation, normal T expressed and secreted (RANTES) is a chemokine that attracts eosinophils, mast cells, and basophils toward site of allergic inflammation. Interferon γ‐inducible protein (IP)‐10 is a Th1‐related chemokine that is also important in asthmatic inflammation and also involved in our immune defense against pathogens. Bronchial epithelial cells are first‐line barrier against invasive pathogen and also have immunomodulatory function. However, whether albuterol and fenoterol (two SABAs) have modulatory effects on RANTES and IP‐10 expression in bronchial epithelial cells is unknown. The human bronchial epithelial cell lines, BEAS‐2B cells, were pre‐treated with different concentrations of albuterol, fenoterol or dibutyryl‐cAMP (a cyclic AMP analog) before polyinosinic‐polycytidylic acid (poly I:C) stimulation. In some condition, BEAS‐2B cells were pre‐treated with ICI‐118551, a selective β2‐adrenoreceptor antagonist, 30 min before albuterol or fenoterol treatment. The levels of RANTES and IP‐10 were measured by ELISA. Intracellular signaling was investigated using cAMP assay, mitogen‐activated protein kinase (MAPK) inhibitor, nuclear factor (NF)‐κB inhibitor, and western blot. Albuterol and fenoterol suppressed poly I:C‐induced RANTES and IP‐10 expression of BEAS‐2B cells. ICI‐118551 could partly reverse the suppressive effects of albuterol and fenoterol on RANTES and IP‐10 expression. Albuterol and fenoterol increased intracellular cAMP levels. Dibutyryl‐cAMP conferred the similar effects of albuterol and fenoterol. Western blot revealed that albuterol suppressed p‐ERK, p‐JNK and pp38, and also their associated kinase expression. Albuterol had no effect on pp65 expression. Albuterol and fenoterol could suppress poly I:C‐induced RANTES and IP‐10 expression in human bronchial epithelial cells via at least partly the β2‐adrenoreceptor‐cAMP and the MAPK pathways, implicating that albuterol and fenoterol could exert anti‐inflammatory effect and benefit asthmatic patients by suppressing RANTES and IP‐10 expression. However, these suppressive effects of albuterol and