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Epigenetic regulation in allergic diseases and related studies.

Kuo CH, Hsieh CC, Lee MS, Chang KT, Kuo HF, Hung CH - Asia Pac Allergy (2014)

Bottom Line: Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes.Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3).However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80708, Taiwan. ; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

ABSTRACT
Asthma, a chronic inflammatory disorder of the airway, has features of both heritability as well as environmental influences which can be introduced in utero exposures and modified through aging, and the features may attribute to epigenetic regulation. Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes. Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3). Therefore, the mechanism by which epigenetic regulation contributes to allergic diseases is a critical issue. In the past most published experimental work, with few exceptions, has only comprised small observational studies and models in cell systems and animals. However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis. Interestingly, a potential link between exposure to environmental pollutants and the occurrence of allergic diseases is revealed recently, particular in developed and industrialized countries, and endocrine disrupting chemicals (EDCs) as environmental hormone may play a key role. This review addresses the important question of how EDCs (nonylphenol, 4 octylphenol, and phthalates) influences on asthma-related gene expression via epigenetic regulation in immune cells, and how anti-asthmatic agents prohibit expression of inflammatory genes via epigenetic modification. The discovery and validation of epigenetic biomarkers linking exposure to allergic diseases might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies.

No MeSH data available.


Related in: MedlinePlus

Immunomodulatory effects of endocrine disrupting chemicals (EDCs) on immune cells. In plasmacytoid dendritic cells (DCs), EDCs activate acryl hydrocarbon receptor (AhR) and inhibit toll-like receptor (TLR)-activated mitogen-activated protein kinases (MAPK)-ERK phosphorylation. EDCs also inhibit H3K4 methyltransferase WDR5 to suppress H3K4 trimethylation at interferon regulatory factor 7 (IRF-7) promoter region and finally suppress the expression of IRF-7, and subsequently inhibit the production of type 1 interferon (IFN)-α and IFN-β. In myeloid DCs, EDCs activate estrogen receptor (ER) and increase phosphorylation of MAPK-p38. EDCs increase H3 and H4 acetylation at tumor necrosis factor alpha (TNF-α) promoter region and increase the production of TNF-α. EDCs enhance the T-cell stimulatory ability of both plasmacytoid and myeloid DCs toward Th2 polarization. On the contrary, EDCs attenuate Th1 polarization. These effects of EDCs on immune cells suggest that EDCs may promote allergic reaction and suppress the immunity against invaded pathogens.
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Figure 1: Immunomodulatory effects of endocrine disrupting chemicals (EDCs) on immune cells. In plasmacytoid dendritic cells (DCs), EDCs activate acryl hydrocarbon receptor (AhR) and inhibit toll-like receptor (TLR)-activated mitogen-activated protein kinases (MAPK)-ERK phosphorylation. EDCs also inhibit H3K4 methyltransferase WDR5 to suppress H3K4 trimethylation at interferon regulatory factor 7 (IRF-7) promoter region and finally suppress the expression of IRF-7, and subsequently inhibit the production of type 1 interferon (IFN)-α and IFN-β. In myeloid DCs, EDCs activate estrogen receptor (ER) and increase phosphorylation of MAPK-p38. EDCs increase H3 and H4 acetylation at tumor necrosis factor alpha (TNF-α) promoter region and increase the production of TNF-α. EDCs enhance the T-cell stimulatory ability of both plasmacytoid and myeloid DCs toward Th2 polarization. On the contrary, EDCs attenuate Th1 polarization. These effects of EDCs on immune cells suggest that EDCs may promote allergic reaction and suppress the immunity against invaded pathogens.

Mentions: The rapid increase in the prevalence of asthma in the world was found over only the past few decades. The huge variations can be observed among populations with a similar racial/ethnic background but different environmental exposures [16], and there is a strong correlation between exposure to environmental pollutants and the occurrence of allergic diseases. Exposure to environmental endocrine-disrupting chemicals (EDCs) is associated with allergy, asthma, chronic inflammation and immunodeficiency via immunomodulatory mechanisms and epigenetic regulations. One of the possible mechanisms for the effect of EDCs on the allergic diseases may result from their impact on antigen-presenting cells and subsequently direct Th2 polarization. For example, nonylphenol and 4 octylphenol may have functional effects on the response of myeloid dendritic cells (DCs) via, in part, the estrogen receptor, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent influence on the T cell-associated cytokine responses in our study [17]. Phthalates, the common environmental hormone used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human plasmacytoid DCs via suppressing IFN-α/IFN-β expression and modulating the ability to stimulate T-cell responses with promotion toward Th2 polarization and suppression toward Th1 polarization [18]. A schematic figure on the effects of EDCs on immune cells is provided (Fig. 1).


Epigenetic regulation in allergic diseases and related studies.

Kuo CH, Hsieh CC, Lee MS, Chang KT, Kuo HF, Hung CH - Asia Pac Allergy (2014)

Immunomodulatory effects of endocrine disrupting chemicals (EDCs) on immune cells. In plasmacytoid dendritic cells (DCs), EDCs activate acryl hydrocarbon receptor (AhR) and inhibit toll-like receptor (TLR)-activated mitogen-activated protein kinases (MAPK)-ERK phosphorylation. EDCs also inhibit H3K4 methyltransferase WDR5 to suppress H3K4 trimethylation at interferon regulatory factor 7 (IRF-7) promoter region and finally suppress the expression of IRF-7, and subsequently inhibit the production of type 1 interferon (IFN)-α and IFN-β. In myeloid DCs, EDCs activate estrogen receptor (ER) and increase phosphorylation of MAPK-p38. EDCs increase H3 and H4 acetylation at tumor necrosis factor alpha (TNF-α) promoter region and increase the production of TNF-α. EDCs enhance the T-cell stimulatory ability of both plasmacytoid and myeloid DCs toward Th2 polarization. On the contrary, EDCs attenuate Th1 polarization. These effects of EDCs on immune cells suggest that EDCs may promote allergic reaction and suppress the immunity against invaded pathogens.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921865&req=5

Figure 1: Immunomodulatory effects of endocrine disrupting chemicals (EDCs) on immune cells. In plasmacytoid dendritic cells (DCs), EDCs activate acryl hydrocarbon receptor (AhR) and inhibit toll-like receptor (TLR)-activated mitogen-activated protein kinases (MAPK)-ERK phosphorylation. EDCs also inhibit H3K4 methyltransferase WDR5 to suppress H3K4 trimethylation at interferon regulatory factor 7 (IRF-7) promoter region and finally suppress the expression of IRF-7, and subsequently inhibit the production of type 1 interferon (IFN)-α and IFN-β. In myeloid DCs, EDCs activate estrogen receptor (ER) and increase phosphorylation of MAPK-p38. EDCs increase H3 and H4 acetylation at tumor necrosis factor alpha (TNF-α) promoter region and increase the production of TNF-α. EDCs enhance the T-cell stimulatory ability of both plasmacytoid and myeloid DCs toward Th2 polarization. On the contrary, EDCs attenuate Th1 polarization. These effects of EDCs on immune cells suggest that EDCs may promote allergic reaction and suppress the immunity against invaded pathogens.
Mentions: The rapid increase in the prevalence of asthma in the world was found over only the past few decades. The huge variations can be observed among populations with a similar racial/ethnic background but different environmental exposures [16], and there is a strong correlation between exposure to environmental pollutants and the occurrence of allergic diseases. Exposure to environmental endocrine-disrupting chemicals (EDCs) is associated with allergy, asthma, chronic inflammation and immunodeficiency via immunomodulatory mechanisms and epigenetic regulations. One of the possible mechanisms for the effect of EDCs on the allergic diseases may result from their impact on antigen-presenting cells and subsequently direct Th2 polarization. For example, nonylphenol and 4 octylphenol may have functional effects on the response of myeloid dendritic cells (DCs) via, in part, the estrogen receptor, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent influence on the T cell-associated cytokine responses in our study [17]. Phthalates, the common environmental hormone used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human plasmacytoid DCs via suppressing IFN-α/IFN-β expression and modulating the ability to stimulate T-cell responses with promotion toward Th2 polarization and suppression toward Th1 polarization [18]. A schematic figure on the effects of EDCs on immune cells is provided (Fig. 1).

Bottom Line: Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes.Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3).However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80708, Taiwan. ; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

ABSTRACT
Asthma, a chronic inflammatory disorder of the airway, has features of both heritability as well as environmental influences which can be introduced in utero exposures and modified through aging, and the features may attribute to epigenetic regulation. Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes. Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3). Therefore, the mechanism by which epigenetic regulation contributes to allergic diseases is a critical issue. In the past most published experimental work, with few exceptions, has only comprised small observational studies and models in cell systems and animals. However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis. Interestingly, a potential link between exposure to environmental pollutants and the occurrence of allergic diseases is revealed recently, particular in developed and industrialized countries, and endocrine disrupting chemicals (EDCs) as environmental hormone may play a key role. This review addresses the important question of how EDCs (nonylphenol, 4 octylphenol, and phthalates) influences on asthma-related gene expression via epigenetic regulation in immune cells, and how anti-asthmatic agents prohibit expression of inflammatory genes via epigenetic modification. The discovery and validation of epigenetic biomarkers linking exposure to allergic diseases might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies.

No MeSH data available.


Related in: MedlinePlus