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.