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Effect of procaterol on Th2‐related chemokines production in human monocyte and bronchial epithelial cells
Author(s) -
Huang ChingHua,
Chu YuTe,
Kuo ChangHung,
Wang WeiLi,
Hua YiMing,
Lee MinSheng,
Hung ChihHsing
Publication year - 2010
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.21275
Subject(s) - chemokine , microbiology and biotechnology , monocyte , immunology , cancer research , medicine , biology , inflammation
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. Pediatr Pulmonol. 2010; 45:977–984. © 2010 Wiley‐Liss, Inc.