Volume 68, Issue 7 pp. 870-879

Original Article

Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation

C.-H. Kuo,

C.-H. Kuo

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung

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C.-C. Hsieh,

C.-C. Hsieh

Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung

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H.-F. Kuo,

H.-F. Kuo

Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung

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M.-Y. Huang,

M.-Y. Huang

Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung

Department of Radiation Oncology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

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S.-N. Yang,

S.-N. Yang

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

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L.-C. Chen,

L.-C. Chen

The Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan

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S.-K. Huang,

S.-K. Huang

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Johns Hopkins Asthma and Allergy Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

National Health Research Institutes, Miaoli County, Taiwan

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C.-H. Hung,

Corresponding Author

C.-H. Hung

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

National Health Research Institutes, Miaoli County, Taiwan

Correspondence

Chih-Hsing Hung, MD, PhD, Department of Pediatrics, Kaohsiung Medical University Hospital, No.100, Tz-You 1st Road, Kaohsiung, Taiwan, Republic of China.

Tel.: 886-7-3121101-6506

Fax: 886-7-3208201

E-mail: [email protected]

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C.-H. Kuo,

C.-H. Kuo

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung

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C.-C. Hsieh,

C.-C. Hsieh

Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung

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H.-F. Kuo,

H.-F. Kuo

Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung

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M.-Y. Huang,

M.-Y. Huang

Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung

Department of Radiation Oncology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

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S.-N. Yang,

S.-N. Yang

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

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L.-C. Chen,

L.-C. Chen

The Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan

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S.-K. Huang,

S.-K. Huang

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Johns Hopkins Asthma and Allergy Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

National Health Research Institutes, Miaoli County, Taiwan

Search for more papers by this author

C.-H. Hung,

Corresponding Author

C.-H. Hung

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung

Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung

National Health Research Institutes, Miaoli County, Taiwan

Correspondence

Chih-Hsing Hung, MD, PhD, Department of Pediatrics, Kaohsiung Medical University Hospital, No.100, Tz-You 1st Road, Kaohsiung, Taiwan, Republic of China.

Tel.: 886-7-3121101-6506

Fax: 886-7-3208201

E-mail: [email protected]

Search for more papers by this author

First published: 05 June 2013

https://doi.org/10.1111/all.12162

Citations: 69

Edited by: Stephan Weidinger

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Abstract

Background

Exposure to environmental endocrine-disrupting chemicals (EDCs) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDCs used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DCs (pDCs) are predominant cells secreting type I interferon (IFN) against infection and are professional antigen-presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDCs are unknown.

Methods

Circulating pDCs were isolated from healthy subjects, were pretreated with diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), and were stimulated with Toll-like receptor (TLR)-9 agonist CpG. IFN-α/IFN-β levels, surface markers, and T-cell stimulatory function were investigated using ELISA, flow cytometry, and pDC/T-cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation.

Results

Diethylhexyl phthalate and butyl benzyl phthalate suppressed CpG-induced IFN-α/IFN-β expression in pDCs, and the effect was reversed by aryl hydrocarbon receptor (AHR) antagonist. Diethylhexyl phthalate suppressed CpG-activated mitogen-activated protein kinase (MAPK)-MEK1/2-ERK-ELK1 and NFκB signaling pathways. Diethylhexyl phthalate suppressed CpG-induced interferon regulatory factor (IRF)-7 expression by suppressing histone H3K4 trimethylation at IRF7 gene promoter region through inhibiting translocation of H3K4-specific trimethyltransferase WDR5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate-treated pDCs suppressed IFN-γ but enhanced IL-13 production by CD4+ T cells.

Conclusion

Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human pDCs via suppressing IFN-α/IFN-β expression and modulating the ability to stimulate T-cell responses.

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Volume68, Issue7

July 2013

Pages 870-879

Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation

Abstract

Background

Methods

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Conclusion

References

Citing Literature

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Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation

Abstract

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Conclusion

References

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