The endocrine disruptors nonylphenol and octylphenol exert direct effects on T cells to suppress Th1 development and enhance Th2 development

Iwata, Makoto; Eshima, Yuko; Kagechika, Hiroyuki; Miyaura, Hideki

doi:10.1016/j.imlet.2004.04.013

Cited by 36 publications

(13 citation statements)

References 16 publications

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“…These findings agree with Lee et al (2003) and Iwata et al (2004) in showing an imbalance of Th1/Th2 cytokines in immune cells caused by p -NP exposure. Specifically, Lee et al (2003) demonstrated that p -NP increased IL-4 production in CD4 + T cells and Iwata et al (2004) showed that p -NP and octylphenol had direct effects on T cells, suppressing the Th1 and enhancing the Th2 cytokine development.…”

Section: Discussionsupporting

confidence: 91%

“…Many studies conducted in humans and mice have established that a correct balance of cytokines at the maternal–fetal interface is an essential requirement for proper placental development and therefore reproductive success (Chaddha et al 2004; Chaouat et al 1990; Cross et al 1994; Laird et al 2006; Raghupathy and Kalinka 2008). Alkylphenols, particularly p -NP, also act in immune T cells by altering cytokine synthesis in mice (Iwata et al 2004; Lee et al 2003, 2004). …”

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confidence: 99%

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Environmental Levels of para -Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

Bechi

Ietta

Romagnoli

et al. 2010

Environ Health Perspect

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Backgroundpara-Nonylphenol (p-NP) is a metabolite of alkylphenols widely used in the chemical industry and manufacturing. It accumulates in the environment, where it acts with estrogen-like activity. We previously showed that p-NP acts on human placenta by inducing trophoblast differentiation and apoptosis.ObjectiveThe aim of the present study was to investigate the effect of p-NP on cytokine secretion in human placenta.MethodsIn vitro cultures of chorionic villous explants from human placenta in the first trimester of pregnancy were treated with p-NP (10−13, 10−11, and 10−9 M) in 0.1% ethanol as vehicle. Culture medium was collected after 24 hr and assayed by specific immunoassays for the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α).Resultsp-NP modulated cytokine secretion by inducing the release of GM-CSF, IFN-γ, IL-1β, IL-4, and IL-10, with a maximum effect at 10−11 M. It reduced the release of TNF-α at 10−13 M, whereas levels of IL-2 and IL-5 remained below the detection limit. IL-6 and IL-8 levels were 100–1,000 times higher than those of other cytokines, and they were not affected by p-NP. We observed significant differences from controls (ethanol alone) only for GM-CSF and IL-10.ConclusionAn unbalanced cytokine network at the maternal–fetal interface may result in implantation failure, pregnancy loss, or other complications. The effects of extremely low doses of p-NP on the placental release of cytokines raise considerable concerns about maternal exposure to this endocrine disruptor during pregnancy.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Environmental Levels of para -Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

Bechi

Ietta

Romagnoli

et al. 2010

Environ Health Perspect

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“…However, a number of sex steroid effects on immune system functions have been described (Watson and Gametchu 2001), although relatively few have been explored mechanistically. Estrogens (10 −7 M E 2 , nonylphenol, and octylphenol) promote a T H 2 response associated with increased IL-4 and decreased interferon-γ (IFN-γ) production from CD4 + CD8 + thymocytes and naive CD4 + T cells isolated from C57BL/6 mice (Iwata et al 2004). Lambert et al (2005), using cells from an ERα knockout mouse on a C57BL/6 background, found that 10 −9 M E 2 acts through ERα to increase IL-4 and GATA-3 expression and essential T H 2 cytokine and transcription factors in CD4 + cells and to reduce IFN-γ production from macrophages.…”

Section: Discussionmentioning

confidence: 99%

Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups

Midoro-Horiuti

Tiwari²,

Watson

et al. 2010

Environ Health Perspect

145

132

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BackgroundWe recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro.ObjectivesWe hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups’ response to allergic sensitization and bronchial challenge.MethodsFemale BALB/c mice received 10 μg/mL BPA in their drinking water from 1 week before impregnation to the end of the study. Neonatal mice were given a single 5 μg intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 min on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique.ResultsNeonates from BPA-exposed mothers responded to this “suboptimal” sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (p < 0.05).ConclusionsPerinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.

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“…It has also been established that NP and OP impair cytokine secretion in the mouse macrophage cell line RAW 264 after exposure of the cells to lipopolysaccharide [5, 17]. NP and OP can suppress the Th1 pathway and enhance the Th2 cell pathway, which results in an imbalanced Th1/Th2 system [7]. NP is capable of inducing apoptosis in Jurkat cells and thymocytes by activating caspase-8 and caspase-3, respectively; it also causes mitochondrial depolarization [16].…”

Section: Discussionmentioning

confidence: 99%

Alkylphenol Polyethoxylate Derivatives in Groundwater and Blood Samples Collected from Pig Herds in Taiwan

Chiu

Hsieh

Miaw

et al. 2014

The Journal of Veterinary Medical Science

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Alkylphenol polyethoxylate (APEO) derivatives, such as nonylphenol monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO), nonylphenol (NP) and octylphenol (OP), have been detected in the surface water, sediment, food and groundwater of numerous countries. Because groundwater is the main source of water for pig herds, the aim of this study was to measure the concentrations of APEO derivatives in groundwater and blood samples that were collected from pig herds raised near the Wuluo River in Southern Taiwan. The mean concentrations of NP, OP, NP1EO and NP2EO in the groundwater supply for 10 pig herds were 0.04 µg/l, 0.26 ± 0.23 µg/l, 0.74 ± 0.69 µg/l and 0.17 ± 0.22 µg/l, respectively. NP was detected in all blood samples collected from 5 of the 10 pig herds. The highest concentrations detected in the blood samples collected from six-week-old piglets and sows were 12.00 µg/l and 56.94 µg/l, respectively. Blood samples from 4 of the 5 herds showed OP contamination. The highest OP concentrations detected in 6-week-old piglets and sows were 275.58 µg/l and 566.32 µg/l, respectively. These results indicate that APEO derivatives accumulated in the groundwater supply and the bloodstreams of the pigs.

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The endocrine disruptors nonylphenol and octylphenol exert direct effects on T cells to suppress Th1 development and enhance Th2 development

Cited by 36 publications

References 16 publications

Environmental Levels of para -Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

Environmental Levels of para -Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups

Alkylphenol Polyethoxylate Derivatives in Groundwater and Blood Samples Collected from Pig Herds in Taiwan

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