Cysteinyl leukotriene receptor antagonist epigenetically modulates cytokine expression and maturation of human myeloid dendritic cells

Chang Hung Kuo, San Nan Yang, Hsuan Fu Kuo, Min Sheng Lee, Ming Yii Huang, Shau Ku Huang, Yi Ching Lin, Chong Chao Hsieh, Chih Hsing Hung

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Cysteinyl leukotriene receptor antagonists are important controllers in treating asthma. Human myeloid DCs (mDCs) play critical roles in the pathogenesis of asthma. However, the effects of cysteinyl leukotriene receptor antagonist on human mDCs are unknown. Methods To investigate the effects of cysteinyl leukotriene receptor antagonist on the function of human mDCs, circulating mDCs were isolated from six health subjects. Human mDCs were pretreated with montelukast and were stimulated with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C). Tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors, western blot and chromatin immunoprecipitation. Costimulatory molecules expression was investigated by flow cytometry. T cell polarization function of mDCs was investigated by measuring interferon (IFN)-γ, IL-13, IL-10 and IL-17A production by T cells using mDC/T cell coculture assay. Results Montelukast suppressed TLR-mediated TNF-α expression via the NFκB-p65 and mitogen-activated protein kinase (MAPK)-JNK pathway, and enhanced TLR-mediated IL-10 expression via the MAPK-p38 pathway and epigenetic regulation by histone H3 acetylation. Montelukast suppressed LPS-induced CD80, CD86, CD40 and HLA-DR expression. Montelukast-treated mDCs suppressed IFN-γ and IL-13 production by T cells. Conclusion Cysteinyl leukotriene receptor antagonist alters the function of human mDCs by epigenetically modulating cytokine expression, suppressing costimulatory molecules expression and inhibiting the ability to initiate Th1/Th2 responses. The effects of cysteinyl leukotriene receptor antagonist on human mDCs can be an important mechanism in treating asthma.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalPulmonary Pharmacology and Therapeutics
Volume39
DOIs
Publication statusPublished - Aug 1 2016
Externally publishedYes

Fingerprint

montelukast
Leukotriene Antagonists
Myeloid Cells
T-cells
Dendritic Cells
Cytokines
Toll-Like Receptors
Interleukin-10
Interleukin-13
T-Lymphocytes
Asthma
Interferons
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Poly I-C
Acetylation
Molecules
Interleukin-17
Flow cytometry
JNK Mitogen-Activated Protein Kinases

Keywords

  • Cysteinyl leukotriene receptor antagonist
  • Dendritic cell
  • Epigenetics
  • Interleukin-10
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Cysteinyl leukotriene receptor antagonist epigenetically modulates cytokine expression and maturation of human myeloid dendritic cells. / Kuo, Chang Hung; Yang, San Nan; Kuo, Hsuan Fu; Lee, Min Sheng; Huang, Ming Yii; Huang, Shau Ku; Lin, Yi Ching; Hsieh, Chong Chao; Hung, Chih Hsing.

In: Pulmonary Pharmacology and Therapeutics, Vol. 39, 01.08.2016, p. 28-37.

Research output: Contribution to journalArticle

Kuo, Chang Hung ; Yang, San Nan ; Kuo, Hsuan Fu ; Lee, Min Sheng ; Huang, Ming Yii ; Huang, Shau Ku ; Lin, Yi Ching ; Hsieh, Chong Chao ; Hung, Chih Hsing. / Cysteinyl leukotriene receptor antagonist epigenetically modulates cytokine expression and maturation of human myeloid dendritic cells. In: Pulmonary Pharmacology and Therapeutics. 2016 ; Vol. 39. pp. 28-37.
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abstract = "Background Cysteinyl leukotriene receptor antagonists are important controllers in treating asthma. Human myeloid DCs (mDCs) play critical roles in the pathogenesis of asthma. However, the effects of cysteinyl leukotriene receptor antagonist on human mDCs are unknown. Methods To investigate the effects of cysteinyl leukotriene receptor antagonist on the function of human mDCs, circulating mDCs were isolated from six health subjects. Human mDCs were pretreated with montelukast and were stimulated with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C). Tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors, western blot and chromatin immunoprecipitation. Costimulatory molecules expression was investigated by flow cytometry. T cell polarization function of mDCs was investigated by measuring interferon (IFN)-γ, IL-13, IL-10 and IL-17A production by T cells using mDC/T cell coculture assay. Results Montelukast suppressed TLR-mediated TNF-α expression via the NFκB-p65 and mitogen-activated protein kinase (MAPK)-JNK pathway, and enhanced TLR-mediated IL-10 expression via the MAPK-p38 pathway and epigenetic regulation by histone H3 acetylation. Montelukast suppressed LPS-induced CD80, CD86, CD40 and HLA-DR expression. Montelukast-treated mDCs suppressed IFN-γ and IL-13 production by T cells. Conclusion Cysteinyl leukotriene receptor antagonist alters the function of human mDCs by epigenetically modulating cytokine expression, suppressing costimulatory molecules expression and inhibiting the ability to initiate Th1/Th2 responses. The effects of cysteinyl leukotriene receptor antagonist on human mDCs can be an important mechanism in treating asthma.",
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T1 - Cysteinyl leukotriene receptor antagonist epigenetically modulates cytokine expression and maturation of human myeloid dendritic cells

AU - Kuo, Chang Hung

AU - Yang, San Nan

AU - Kuo, Hsuan Fu

AU - Lee, Min Sheng

AU - Huang, Ming Yii

AU - Huang, Shau Ku

AU - Lin, Yi Ching

AU - Hsieh, Chong Chao

AU - Hung, Chih Hsing

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Background Cysteinyl leukotriene receptor antagonists are important controllers in treating asthma. Human myeloid DCs (mDCs) play critical roles in the pathogenesis of asthma. However, the effects of cysteinyl leukotriene receptor antagonist on human mDCs are unknown. Methods To investigate the effects of cysteinyl leukotriene receptor antagonist on the function of human mDCs, circulating mDCs were isolated from six health subjects. Human mDCs were pretreated with montelukast and were stimulated with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C). Tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors, western blot and chromatin immunoprecipitation. Costimulatory molecules expression was investigated by flow cytometry. T cell polarization function of mDCs was investigated by measuring interferon (IFN)-γ, IL-13, IL-10 and IL-17A production by T cells using mDC/T cell coculture assay. Results Montelukast suppressed TLR-mediated TNF-α expression via the NFκB-p65 and mitogen-activated protein kinase (MAPK)-JNK pathway, and enhanced TLR-mediated IL-10 expression via the MAPK-p38 pathway and epigenetic regulation by histone H3 acetylation. Montelukast suppressed LPS-induced CD80, CD86, CD40 and HLA-DR expression. Montelukast-treated mDCs suppressed IFN-γ and IL-13 production by T cells. Conclusion Cysteinyl leukotriene receptor antagonist alters the function of human mDCs by epigenetically modulating cytokine expression, suppressing costimulatory molecules expression and inhibiting the ability to initiate Th1/Th2 responses. The effects of cysteinyl leukotriene receptor antagonist on human mDCs can be an important mechanism in treating asthma.

AB - Background Cysteinyl leukotriene receptor antagonists are important controllers in treating asthma. Human myeloid DCs (mDCs) play critical roles in the pathogenesis of asthma. However, the effects of cysteinyl leukotriene receptor antagonist on human mDCs are unknown. Methods To investigate the effects of cysteinyl leukotriene receptor antagonist on the function of human mDCs, circulating mDCs were isolated from six health subjects. Human mDCs were pretreated with montelukast and were stimulated with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C). Tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors, western blot and chromatin immunoprecipitation. Costimulatory molecules expression was investigated by flow cytometry. T cell polarization function of mDCs was investigated by measuring interferon (IFN)-γ, IL-13, IL-10 and IL-17A production by T cells using mDC/T cell coculture assay. Results Montelukast suppressed TLR-mediated TNF-α expression via the NFκB-p65 and mitogen-activated protein kinase (MAPK)-JNK pathway, and enhanced TLR-mediated IL-10 expression via the MAPK-p38 pathway and epigenetic regulation by histone H3 acetylation. Montelukast suppressed LPS-induced CD80, CD86, CD40 and HLA-DR expression. Montelukast-treated mDCs suppressed IFN-γ and IL-13 production by T cells. Conclusion Cysteinyl leukotriene receptor antagonist alters the function of human mDCs by epigenetically modulating cytokine expression, suppressing costimulatory molecules expression and inhibiting the ability to initiate Th1/Th2 responses. The effects of cysteinyl leukotriene receptor antagonist on human mDCs can be an important mechanism in treating asthma.

KW - Cysteinyl leukotriene receptor antagonist

KW - Dendritic cell

KW - Epigenetics

KW - Interleukin-10

KW - Tumor necrosis factor-α

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