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http://ir.nhri.org.tw/handle/3990099045/5536
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| Title: | Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation |
| Authors: | Kuo, CH;Ko, YC;Yang, SN;Chu, YT;Wang, WL;Huang, SK;Chen, HN;Wei, WJ;Jong, YJ;Hung, CH |
| Contributors: | Division of Environmental Health and Occupational Medicine |
| Abstract: | Chemokines play important roles in asthma. Prostaglandin I-2 (PGI(2)) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI(2) analogues on the expression of Th1- and Th2-related chemokincs are unknown. To this end, we investigated the in vitro effects of PGI(2) analogues on the expression of Th1-related chemokine interferon-gamma-inducible protein-10 (IP-10/CXCL10) and Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) in human monocytes. The human monocytes were pretreated with iloprost and treprostinil before lipopolysaccharide (LPS) stimulation. IP-10 and MDC were measured by ELISA. Intracellular signaling was investigated by cyclic adenosine monophosphate (cAMP) assay, western blot and chromatin immunoprecipitation. PGI(2) analogues enhanced MDC, but suppressed IP-10 expression in LPS-stimulated monocytes. These effects were reversed by the I prostanoid (IP) receptor antagonist (CAY10449), peroxisomal proliferators-activated receptor (PPAR)-alpha antagonist (GW6741) and PPAR-gamma antagonist (GW9662). PGI(2) analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI(2) analogue-enhanced MDC expression was reduced by nuclear factor (NF) kappa B inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI(2) analogues up-regulated phospho-p65 and phospho-p38 but down-regulated phospho-ERK expression. Iloprost enhanced H3 acetylation in MDC promoter area and suppressed H3 acetylation, H3K4, and H3K36 trimethylation in IP-10 promoter area. PGI(2) analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-alpha and PPAR-gamma, NF kappa B-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-gamma, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI(2) analogues may therefore increase Th2 recruitment and inflammation. |
| Date: | 2011-01 |
| Relation: | Journal of Molecular Medicine. 2011 Jan;89(1):29-41. |
| Link to: | http://dx.doi.org/10.1007/s00109-010-0694-2 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0946-2716&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000288363200005 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78651374332 |
| Appears in Collections: | [葛應欽(2003-2009)] 期刊論文
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| ISI000288363200005.pdf | | 756Kb | Adobe PDF | 636 | View/Open |
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