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Diverse Influences of Androgen-Disrupting Chemicals on Immune Responses Mounted by Macrophages

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Abstract

Androgen-disrupting chemicals (ADCs) can alter male sexual development. Although the effects of ADCs on hormone disruption have been studied, their influence on the immune response is not fully understood. To investigate the effects of ADCs on innate immunity, we tested eight candidate ADCs for their influence on macrophages by measuring nitric oxide (NO) production and cell viability. Our results showed that treatment with a mixture of lipopolysaccharide and hexachlorobenzene increased NO production in RAW 264.7 cells, a murine macrophage cell line. In contrast, compared to exposure to a negative control, exposure to di-2-ethylhexyl adipate (DEHA), benzylbutyl phthalate (BBP), testosterone (TTT), or permethrin decreased NO production. DEHA, BBP, and TTT inhibited NO production in an inducible nitric oxide synthase-dependent manner. Treatment with bisphenol A (BPA), nonylphenol (NNP), or tributyltin chloride (TBTC) reduced NO production and induced cell death. While BPA induced RAW 264.7 cell death through apoptosis, NNP and TBTC caused cell death through necrosis. These results offer insights into the influences of ADCs on the innate immune system.

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Abbreviations

ADCs:

Androgen-disrupting chemicals

BPA:

Bisphenol A

BBP:

Benzylbutyl phthalate

DEHA:

Di-2-ethylhexyl adipate

HCB:

Hexachlorobenzene

NNP:

Nonylphenol

PMT:

Permethrin

TTT:

Testosterone

TBTC:

Tributyltin chloride

LPS:

Lipopolysaccharide

NO:

Nitric oxide

iNOS:

Inducible nitric oxide synthase

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Acknowledgments

We appreciate Drs. Young-Ho Jeon and Young In Park for their critical comments. We also thank Moon Hwan Oh, Ju Hyung Lee, Sang Hyun Jo, and Hye Young Cho for their technical support. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0012178), by the BK21 plus program of the Ministry of Education, by the MSIP (Ministry of Science, ICT&Future Planning, 122S-4-3-0434), and by the financial support of Next-Generation BioGreen 21 Program (PJ009508) from the Rural Development Administration, Republic of Korea.

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Authors and Affiliations

  1. Department of Biotechnology and Bioinformatics, Korea University, Sejong, 339-700, Republic of Korea

    Kyong Hoon Kim, Seung Pil Pack & Un-Hwan Ha

  2. Department of Pharmacy, Korea University, Sejong, 339-700, Republic of Korea

    Seung-min Yeon, Hyun Gyung Kim, Hyun Suk Choi, Eun Hee Lee, Youngjoo Byun, Sang-Eun Choi, Kenneth Sung Lee & Yong Woo Jung

  3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 702-701, Republic of Korea

    Hyojeung Kang

  4. School of Civil, Environmental and Architectural Engineering, Korea University, Seoul, 136-713, Republic of Korea

    Hee-Deung Park

  5. Department of Psychiatry, Chonbuk National University Medical School, Jeonju, 561-712, Republic of Korea

    Tae Won Park

  6. Department of Chemistry and Biochemistry, Jackson State University, 1325 J. R. Lynch Street, Jackson, MS, 39217, USA

    Kenneth Sung Lee

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  1. Kyong Hoon Kim
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Corresponding authors

Correspondence to Un-Hwan Ha or Yong Woo Jung.

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Kyong Hoon Kim and Seung-min Yeon contributed equally.

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Kim, K.H., Yeon, Sm., Kim, H.G. et al. Diverse Influences of Androgen-Disrupting Chemicals on Immune Responses Mounted by Macrophages. Inflammation 37, 649–656 (2014). https://doi.org/10.1007/s10753-013-9781-1

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