Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation

Chang Hung Kuo; Ying Chin Ko; San Nan Yang; Yu Te Chu; Wei Li Wang; Shau Ku Huang; Huan Nan Chen; Wan Ju Wei; Yuh Jyh Jong; Chih Hsing Hung

doi:10.1007/s00109-010-0694-2

Effects of PGI₂ analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation

Chang Hung Kuo
, Ying Chin Ko
, San Nan Yang
, Yu Te Chu
, Wei Li Wang
, Shau Ku Huang
, Huan Nan Chen
, Wan Ju Wei
, Yuh Jyh Jong
, Chih Hsing Hung^*

^*Corresponding author for this work

Kaohsiung Municipal Ta-Tung Hospital
Kaohsiung Medical University
National Health Research Institutes Taiwan
Johns Hopkins University

Research output: Contribution to journal › Journal Article › peer-review

38 Scopus citations

Abstract

Chemokines play important roles in asthma. Prostaglandin I₂ (PGI₂) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI₂ analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI₂ analogues on the expression of Th1-related chemokine interferon-γ-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. PGI₂ 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)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI₂ analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI₂ analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI₂ 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. PGI₂ analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI₂ analogues may therefore increase Th2 recruitment and inflammation.

Original language	English
Pages (from-to)	29-41
Number of pages	13
Journal	Journal of Molecular Medicine
Volume	89
Issue number	1
DOIs	https://doi.org/10.1007/s00109-010-0694-2
State	Published - 01 2011
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Epigenetics
Interferon-γ-inducible protein-10
Macrophage-derived chemokine
Monocytes
Prostaglandin I

Access to Document

10.1007/s00109-010-0694-2

Cite this

@article{2acc31a12ee24aeb8445b0c39d499fc4,

title = "Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation",

abstract = "Chemokines play important roles in asthma. Prostaglandin I2 (PGI2) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI2 analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI2 analogues on the expression of Th1-related chemokine interferon-γ-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. PGI2 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)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI2 analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI2 analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI2 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. PGI2 analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI2 analogues may therefore increase Th2 recruitment and inflammation.",

keywords = "Epigenetics, Interferon-γ-inducible protein-10, Macrophage-derived chemokine, Monocytes, Prostaglandin I",

author = "Kuo, \{Chang Hung\} and Ko, \{Ying Chin\} and Yang, \{San Nan\} and Chu, \{Yu Te\} and Wang, \{Wei Li\} and Huang, \{Shau Ku\} and Chen, \{Huan Nan\} and Wei, \{Wan Ju\} and Jong, \{Yuh Jyh\} and Hung, \{Chih Hsing\}",

year = "2011",

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doi = "10.1007/s00109-010-0694-2",

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T1 - Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation

AU - Kuo, Chang Hung

AU - Ko, Ying Chin

AU - Yang, San Nan

AU - Chu, Yu Te

AU - Wang, Wei Li

AU - Huang, Shau Ku

AU - Chen, Huan Nan

AU - Wei, Wan Ju

AU - Jong, Yuh Jyh

AU - Hung, Chih Hsing

PY - 2011/1

Y1 - 2011/1

N2 - Chemokines play important roles in asthma. Prostaglandin I2 (PGI2) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI2 analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI2 analogues on the expression of Th1-related chemokine interferon-γ-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. PGI2 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)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI2 analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI2 analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI2 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. PGI2 analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI2 analogues may therefore increase Th2 recruitment and inflammation.

AB - Chemokines play important roles in asthma. Prostaglandin I2 (PGI2) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI2 analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI2 analogues on the expression of Th1-related chemokine interferon-γ-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. PGI2 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)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI2 analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI2 analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI2 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. PGI2 analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI2 analogues may therefore increase Th2 recruitment and inflammation.

KW - Epigenetics

KW - Interferon-γ-inducible protein-10

KW - Macrophage-derived chemokine

KW - Monocytes

KW - Prostaglandin I

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U2 - 10.1007/s00109-010-0694-2

DO - 10.1007/s00109-010-0694-2

M3 - 文章

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