The Effects of Endocrine Disrupting Chemicals on Biomarkers of Inflammation Produced by Lipopolysaccharide Stimulated RAW264.7 Macrophages.

Edmund J. Pool,Vedastus W. Makene

doi:10.3390/ijerph16162914

Edmund J. Pool, Vedastus W. Makene

Open Access

https://doi.org/10.3390/ijerph16162914

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Abstract

Endocrine disrupting chemicals (EDCs) are common pollutants in the environment and can induce disruption of the endocrine and immune systems. The present study evaluated the effects of selected common environmental EDCs on secretion of inflammatory biomarkers by RAW264.7 cells. The EDCs investigated were Estradiol (E2), 5α-dihydrotestosterone (DHT), and Bisphenol A (BPA). To evaluate if the effects caused by EDCs were modulated by steroid hormone receptors, antagonists of estrogen and androgen receptors were used. The steroid receptor antagonists used were Tamoxifen, an estrogen receptor antagonist, and Flutamide, an androgen receptor antagonist. Secretion of biomarkers of inflammation, namely nitric oxide (NO) and interleukin 6 (IL-6), were monitored. The NO was determined using Griess reaction and IL-6 was measured by enzyme linked immunosorbent assay (ELISA). Although 5 μg/mL E2, DHT, and BPA were not toxic to RAW264.7 cell cultures, the same treatments significantly (p < 0.001) reduced both NO and IL-6 secretion by lipopolysaccharide (LPS)-stimulated RAW264.7 cell cultures. The suppression of NO and IL-6 secretion indicate inhibition of inflammation by DHT, E2, and BPA. The inhibitory effects of DHT, E2 and BPA are partially mediated via their cellular receptors, because the effects were reversed by their respective receptor antagonists. Flutamide reversed the effects of DHT, while Tamoxifen reversed the effects of E2 and BPA. In conclusion, E2, BPA, and DHT inhibit the synthesis of inflammation biomarkers by LPS-stimulated RAW264.7 cells. The inhibitory effects of EDCs can be partially reversed by the addition of an estrogen receptor antagonist for E2 and BPA, and an androgenic receptor antagonist for DHT. The inhibition of inflammatory response in stimulated RAW264.7 cells may be a useful bioassay model for monitoring estrogenic and androgenic pollutants.

Highlights

Endocrine disrupting chemicals (EDCs) are environmental compounds that can interfere with biosynthesis, secretion, action, or metabolism of endogenous hormones, resulting in altered normal hormone actions [1,2]
This study evaluated whether effects of the EDCs on inflammatory biomarkers are mediated via their respective steroid receptors
Based on the possible effects of estrogenic and androgenic compounds on the immune system, the present study evaluated whether exposure of macrophages to common EDCs such as DHT, E2, and Bisphenol A (BPA) modulate inflammatory biomarker production

Summary

Introduction

Endocrine disrupting chemicals (EDCs) are environmental compounds that can interfere with biosynthesis, secretion, action, or metabolism of endogenous hormones, resulting in altered normal hormone actions [1,2]. They include compounds such as industrial chemicals, agricultural chemicals like pesticides, natural and synthetic hormones, and pharmaceuticals. These chemicals are widely distributed in the environment and especially in wastewater. While BPA is an industrial chemical with many applications, testosterone and E2 are natural hormones of male and female animals, respectively. Public Health 2019, 16, 2914; doi:10.3390/ijerph16162914 www.mdpi.com/journal/ijerph

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