title: Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells.
abstract: 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 fenoterol may inhibit the defense against viral infection.
authors.affiliation: Department of Pediatrics, Pingtung Christian Hospital, Pingtung, Taiwan.
authors.forename: Ka-Pan
authors.initials: KP
authors.lastname: Lam
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Chu
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Lee
authors.forename: Huan-Nan
authors.initials: HN
authors.lastname: Chen
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Wang
authors.forename: Teck-Siang
authors.initials: TS
authors.lastname: Tok
authors.forename: Yow-Yue
authors.initials: YY
authors.lastname: Chin
authors.forename: Solomon Chih-Cheng
authors.initials: SC
authors.lastname: Chen
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001386:Azides / Q000494:pharmacology / Q000627:therapeutic use; D001980:Bronchi / Q000473:pathology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005280:Fenoterol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001386:Azides; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D011412:Propanolamines; D005280:Fenoterol; D012701:Serotonin; C026777:ICI 118551; C046122:3-(2-(4-azidobenzamidino)ethyl)-5-hydroxyindole; D000242:Cyclic AMP; D011070:Poly I-C; D000420:Albuterol