title: Effect of procaterol on Th2-related chemokines production in human monocyte and bronchial epithelial cells.
abstract: Procaterol is a β2-adrenoceptor agonist used as a bronchodilator for the treatment of asthma; it also possesses an anti-inflammatory property. As chemokines play a pivotal role in inflammation and the pathogenesis of asthma, we investigated the effects of procaterol on type 2 helper T cell (Th2)-related [macrophage-derived chemokine (MDC) and I-309] and type 1 helper T cell (Th1)-related chemokines [monokine-induced by IFN-gamma (Mig) and interferon-inducible protein 10 (IP-10)] production of THP-1 cells and human primary monocytes. The effect on thymus- and activation-regulated chemokine (TARC) production in BEAS-2B cells was also evaluated. Nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) inhibitors were used to ascertain the intracellular signal pathways involved, and etazolate, a phosphodiesterase 4 inhibitor, was used to assess the correlation between the β2-adrenoceptor-cAMP pathway and the effect on chemokines. In addition, chromatin immunoprecipitation assays (ChIPs) were performed to detect histone modification in the TARC promoter region. MDC and I-309 production of both THP-1 cells and primary human monocytes, as well as TARC expression of BEAS-2B cells, were significantly inhibited by procaterol (10(-10)-10(-7) M); however, procaterol did not suppress Mig and IP-10 expression by THP-1 cells. MDC secreted by monocytes is associated with the NF-κB and MAPK signaling pathways, in particular p38- and c-Jun N-terminal kinase (JNK) MAPKs. Etazolate blocked the expression of MDC by THP-1 cells and TARC by BEAS-2B cells. ChIP assay revealed decreased trimethylation of lysine 4 in histone 3 (H3K4) in the TARC promoter region of BEAS-2B cells. In conclusion, procaterol could inhibit Th2-related chemokines production in human monocytes and bronchial epithelial cells, an effect that may be mediated through not only the NF-κB, p38, and JNK-MAPK pathways, but also the β2-adrenoceptor-cAMP pathway. Most importantly, the suppressive effect of Th2-related chemokines production by procaterol might be regulated via post-transcriptional modification by decreasing H3K4 trimethylation.
authors.affiliation: Department of Pediatrics, Yuan's General Hospital, Taiwan, ROC.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Huang
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: Yi-Ming
authors.initials: YM
authors.lastname: Hua
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Lee
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017265:Procaterol / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018925:Chemokines; D017265:Procaterol