Basic research Environmental toxin 4-nonylphenol and autoimmune diseases: using DNA microarray to examine genetic markers of cytokine expression

Neuroscience Research Institute, State University of New York, College at Old Westbury, Old Westbury, USA.
Archives of medical science : AMS 06/2010; 6(3):321-7. DOI: 10.5114/aoms.2010.14250
Source: PubMed

ABSTRACT Adverse progression of autoimmune diseases is linked to the dysregulation of cytokines. In this regard we investigated the role of 4-nonylphenol (4-NP), as a potential contributing factor in the development of immune diseases and compared it to estrogens actions since 4-NP may work via estrogen processes.
The study made cytokine level expression changes in U937 cells by microarray technology coupled to RT PCR as a validating technique.
It was determined that 4-NP significantly up-regulated proinflammatory cytokine expression (toll-like-receptor [TLR]-6, TLR-10, interleukin [IL]-1, IL-5, IL-6, IL-17C, IL-23A, IL-8RB, IL-receptor-associated-kinase [IRAK-2], tumor-necrosis-factor-receptor [TNFR]-5, and TNFR-10). Estrogen caused insignificant increases but the changes parralelled that of 4-NP. Simultaneously, 4-NP down-regulated the expression of anti-inflammatory cytokines (IL-4 and IL-10), while estrogen up-regulated them.
4-Nonylphenol may initiate its toxic effects and pose a risk to autoimmunity-prone individuals by eliciting effects up to 4 times more potent than estrogen. Overall, exposure to 4-NP may contribute to autoimmune susceptibility and/or exacerbate existing autoimmune conditions by dys-regulating normal expression of cytokines.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The accurate and high-throughput detection of drug resistance-related multiple point mutations remains a challenge. Although the combination of molecular beacons with bio-immobilization technology, such as microarray, is promising, its application is difficult due to the ineffective immobilization of molecular beacons on the chip surface. Here, we propose a novel asymmetric-loop molecular beacon in which the loop consists of 2 parts. One is complementary to a target, while the other is complementary to an oligonucleotide probe immobilized on the chip surface. With this novel probe, a two-phase hybridization assay can be used for simultaneously detecting multiple point mutations. This assay will have advantages, such as easy probe availability, multiplex detection, low background, and high-efficiency hybridization, and may provide a new avenue for the immobilization of molecular beacons and high-throughput detection of point mutations.
    Medical science monitor: international medical journal of experimental and clinical research 04/2012; 18(4):HY5-8. DOI:10.12659/MSM.882602 · 1.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nonylphenol (NP) is the final biodegradation product of nonylphenol polyethoxylates, which are widely used as surfactants in domestic and industrial products. NP was reported to exert estrogenic actions and shown to potentially adversely affect reproductive functions. However, NP influence on immune system function remains unclear. To address this issue, the effects of NP on spleen and thymus were examined in this study. Female Sprague-Dawley rats were treated with NP orally at doses of 0, 20, 80, or 200 mg/kg respectively. Data showed that NP increased the levels of natural killer (NK) cells and natural killer T (NKT) cells in peripheral blood and decreased the levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ) in serum. These findings suggest that exposure to NP by oral route may induce adverse effects on the spleen and thymus and affect the immune function of female rats.
    Toxicological and Environmental Chemistry 04/2013; 95(4). DOI:10.1080/02772248.2013.792987 · 0.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background 4-Nonylphenol is a ubiquitous environmental toxin that is formed as a byproduct in the manufacturing and/or sewage treatment of regular household items. Previous work in our lab has implicated 4-NP in the progression of autoimmune diseases such as inflammatory bowel disease in which macrophages mistakenly attack the intestinal linings, causing chronic inflammation. Several key pro-and anti-inflammatory molecules have been shown to be involved in the manifestation of this disease, including IL-23A, COX-2, IL-8, TLR-4, and IL-10. Material/Methods 4-NP’s effects on these known mediators of IBD were effectively analyzed using a novel model for IBD, by which 4-NP may promote an inflammatory response. Data were collected using DNA Microarray, RT-PCR, and ELISA, after 48 hour treatment of U937 histiocytic lymphocyte cells and COLO320DM human intestinal epithelial cells with 1 nM and 5 nM concentrations of 4-NP. Results Significant dysregulation of the expression of both pro- and anti-inflammatory genes was observed in U937 cells that would promote and prolong inflammation. However, TLR-4, IL-8, and COX-2 gene expressions showed unprecedented effects in COLO320DM cells suggesting that these genes mediate apoptotic processes within the gastrointestinal tract. Conclusions Overall, our results suggest that 4-NP administration engenders immune responses linked to apoptotic processes via dysregulation of macrophage signaling. In sum, 4-NP appears to increases the risk of developing inflammatory bowel disease by promoting or prolonging adverse progression of inflammation in the gastrointestinal tract.
    04/2014; 20:47-54. DOI:10.12659/MSMBR.890644
Show more

Preview (2 Sources)

Available from