title: Effects of formoterol and salmeterol on the production of Th1- and Th2-related chemokines by monocytes and bronchial epithelial cells.
abstract: It is unknown whether formoterol and salmeterol, two long-acting beta(2)-adrenoreceptor agonists, have regulatory functions in the production of T-helper cell (Th) type 2- and Th1-related chemokines by monocytes and bronchial epithelial cells. In the present study, the effects of formoterol and salmeterol on lipopolysaccharide (LPS)-induced expression of the Th2-related chemokine macrophage-derived chemokine (MDC; CCL22) and the Th1-related chemokine interferon-gamma-inducible protein (IP)-10 (CXCL10) were investigated in a monocytic cell line, THP-1, and in human primary monocytes. In addition, their effects on the expression of the Th2-related chemokine thymus- and activation-regulated chemokine (TARC; CCL17) were evaluated in an epithelial cell line, BEAS-2B. Formoterol enhanced MDC but suppressed IP-10 production in monocytes induced by LPS. Higher doses of salmeterol were required to enhance LPS-induced MDC expression in THP-1 cells. Formoterol and salmeterol could significantly suppress TARC expression in BEAS-2B cells. These effects could be reversed by a selective beta(2)-adrenoreceptor antagonist, ICI-118551. Formoterol- and LPS-induced MDC expression was inhibited by budesonide. Both long-acting beta(2)-adrenoreceptor agonists suppressed thymus- and activation-regulated chemokine expression in bronchial epithelial cells mediated via beta(2)-adrenoreceptors. Formoterol at physiological concentrations could suppress lipopolysaccharide-induced T-helper cell type 1-related chemokine (interferon-gamma-inducible protein-10) but enhance T-helper cell type 2-related chemokine (macrophage-derived chemokine) expression in human monocytes. Long-acting beta(2)-adrenoreceptor agonists may increase T-helper cell type 2-related chemokine expression in monocytes and T-helper cell type 2 recruitment and, therefore, long-acting beta(2)-adrenoreceptor agonist monotherapy may not be an appropriate therapeutic option for asthma.
authors.affiliation: Dept of Paediatrics, Faculty of Paediatrics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: C-H
authors.initials: CH
authors.lastname: Hung
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chu
authors.forename: Y-M
authors.initials: YM
authors.lastname: Hua
authors.forename: S-H
authors.initials: SH
authors.lastname: Hsu
authors.forename: C-S
authors.initials: CS
authors.lastname: Lin
authors.forename: H-C
authors.initials: HC
authors.lastname: Chang
authors.forename: M-S
authors.initials: MS
authors.lastname: Lee
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Jong
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; C106230:CCL17 protein, human; C114753:CXCL10 protein, human; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D018925:Chemokines; D004983:Ethanolamines; D025521:Tumor Suppressor Proteins; D000068299:Salmeterol Xinafoate; D051722:ADAM Proteins; C090222:ADAM11 protein, human; D000420:Albuterol; D000068759:Formoterol Fumarate