Modulation of Cytokine Expression in Human Myeloid Dendritic Cells by Environmental Endocrine-Disrupting Chemicals Involves Epigenetic Regulation
| Autor: | Yuh-Jyh Jong, Yu Te Chu, Chih Hsing Hung, Wan Ju Wei, San Nan Yang, Po-Lin Kuo, Shau Ku Huang, Hui Wen Chang |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
MLL
Adult Myeloid dendritic cell MAP Kinase Signaling System T-Lymphocytes Health Toxicology and Mutagenesis medicine.medical_treatment Endocrine Disruptors Biology Epigenesis Genetic Histones Interferon-gamma Young Adult Phenols medicine Humans Myeloid Cells Epigenetics endocrine-disrupting chemical Interleukin-13 nonylphenol Tumor Necrosis Factor-alpha Research Public Health Environmental and Occupational Health Dendritic Cells Dendritic cell Middle Aged Coculture Techniques Interleukin-10 Cell biology Interleukin 10 medicine.anatomical_structure Cytokine Receptors Estrogen Endocrine disruptor Immunology Interleukin 13 Cytokines Environmental Pollutants Signal transduction epigenetic mixed-lineage leukemia Signal Transduction |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| DOI: | 10.1289/ehp.0901011 |
| Popis: | Background Exposure to environmental endocrine-disrupting chemicals (EDCs) is often associated with dysregulated immune homeostasis, but the mechanisms of action remain unclear. Objectives The aim of this study was to test a hypothesis that EDCs regulate the functions of human dendritic cells, a front-line, immunoregulatory cell type in contact with the environment. Methods We investigated circulating myeloid dendritic cells (mDCs) from five subjects and measured their responses, with or without coculture with autologous T cells, to two common EDCs, nonylphenol (NP) and 4-octylphenol (4-OP). EDC-associated cytokine responses, signaling events, and histone modifications were examined using ELISA, Western blotting, and chromatin immunoprecipitation (ChIP) assays, respectively. Results In all cases, mDCs treated with NP or 4-OP demonstrated increased expression of tumor necrosis factor-α (TNF-α) but decreased baseline and lipopolysaccharide (LPS)-induced (interleukin) (IL)-10 production; the increase in TNF-α was partially reversible by an estrogen receptor (ER) antagonist. Activation of the MKK3/6-p38 signaling pathway marked the effect of NP on TNF-α expression, concomitant with enhanced levels of methyltranferase complex [mixed-lineage leukemia (MLL) and tryptophan-aspartic acid repeat domain 5 (WDR5)] in the nucleus and of trimethylated H3K4, acetylated H3, and H4 at the TNFA gene locus. Further, up-regulated TNF-α expression was significantly suppressed in NP-treated mDCs by a histone acetyltransferase inhibitor. In the presence of NP-treated mDCs, T cells showed increased levels of IL-13 but decreased expression of interferon-γ. Conclusions These results suggest that NP and 4-OP may have functional effects on the response of mDCs via, in part, the ER, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent influence on the T-cell cytokine responses. |
| Databáze: | OpenAIRE |
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