title: Suppressive effects of procaterol on expression of IP-10/CXCL 10 and RANTES/CCL 5 by bronchial epithelial cells.
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.
authors.affiliation: Department of Pediatrics, Pingtung Christian Hospital, Pingtung, Taiwan, Republic of China.
authors.forename: Ka-Pan
authors.initials: KP
authors.lastname: Lam
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Chu
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
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: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011070:Poly I-C / Q000494:pharmacology; D017265:Procaterol / Q000378:metabolism / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019892:eIF-2 Kinase / Q000096:biosynthesis
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D016328:NF-kappa B; D011412:Propanolamines; C026777:ICI 118551; D003994:Bucladesine; D019892:eIF-2 Kinase; D020928:Mitogen-Activated Protein Kinases; D011070:Poly I-C; D017265:Procaterol