Estrogenic Endocrine-Disrupting Chemicals Modulate the Production of Inflammatory Mediators and Cell Viability of Lipopolysaccharide-Stimulated Macrophages

Hyun Gyung Kim, Seung min Yeon, Kyong Hoon Kim, Heejoong Kim, Jong Il Park, Hyun Jin Kang, Eun Ji Cha, Hee-Deung Park, Hyo Jung Kang, Tae Won Park, Young Ho Jeon, Young In Park, Kyu Tae Chang, Yong Woo Jung

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Abstract

Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-α-ethynylestradiol, 17-β-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages.

Original languageEnglish
Pages (from-to)595-605
Number of pages11
JournalInflammation
Volume38
Issue number2
DOIs
Publication statusPublished - 2015

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Keywords

  • cell death
  • estrogenic endocrine-disrupting chemical
  • macrophage
  • nitric oxide
  • proinflammatory cytokine

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Kim, H. G., Yeon, S. M., Kim, K. H., Kim, H., Park, J. I., Kang, H. J., Cha, E. J., Park, H-D., Kang, H. J., Park, T. W., Jeon, Y. H., In Park, Y., Chang, K. T., & Jung, Y. W. (2015). Estrogenic Endocrine-Disrupting Chemicals Modulate the Production of Inflammatory Mediators and Cell Viability of Lipopolysaccharide-Stimulated Macrophages. Inflammation, 38(2), 595-605. https://doi.org/10.1007/s10753-014-9966-2