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MAPK and NF-κB Pathways Are Involved in Bisphenol A-Induced TNF-α and IL-6 Production in BV2 Microglial Cells

Inflammation volume 38, pages 637–648 (2015)Cite this article

Abstract

Microglial activation has been reported to play an important role in neurodegenerative diseases by producing pro-inflammatory cytokines. Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl) propane), known as a ubiquitous endocrine-disrupting chemical, is reported to perform both mimic- and anti-estrogen properties; however, whether it affects cytokine production or immune response in central nervous system remains unclear. The present study was aimed to explore whether BPA was involved in inflammatory action and to investigate the potential mechanisms in microglial cells. BV2, the murine microglial cell line, was used in the present work as the cell model. BPA-associated morphologic changes, cytokine responses, and signaling events were examined using immunofluorescence analysis, real-time PCR, enzyme-linked immunosorbent assay, and western blot. Our results indicated that BPA increased BV2 cells activation and simultaneously elevated tumor necrosis factor-α and interleukin 6 expression, which could be partially reversed by estrogen receptor antagonist, ICI182780. In addition, the c-Jun N-terminal protein kinase (JNK) inhibitor (SP600125), rather than ERK1/2 blocker (PD98059), displayed anti-inflammatory properties on BPA-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-κB was specifically activated by BPA as well. These results, taken together, suggested that BPA may have functional effects on the response of microglial cell activation via, in part, the estrogen receptor, JNK, ERK mitogen-activated protein kinase, and NF-κB signaling pathways with its subsequent influence on pro-inflammatory action.

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ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (81273115, 81072329, and 81202230) and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

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Affiliations

  1. Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu, 211166, China

    Jingying Zhu, Yanqing Liu, Wenyi Qian, Jing Zhou, Rong Gao, Hang Xiao & Jun Wang

  2. Department of Experimental Medicine, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu, 210000, China

    Jingli Liu

  3. Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China

    Lei Jiang

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  1. Jingying Zhu
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  2. Lei Jiang
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  3. Yanqing Liu
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Correspondence to Hang Xiao or Jun Wang.

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Jingying Zhu and Lei Jiang have contributed equally to this study.

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Zhu, J., Jiang, L., Liu, Y. et al. MAPK and NF-κB Pathways Are Involved in Bisphenol A-Induced TNF-α and IL-6 Production in BV2 Microglial Cells. Inflammation 38, 637–648 (2015). https://doi.org/10.1007/s10753-014-9971-5

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KEY WORDS

  • bisphenol A
  • immunomodulatory cytokines
  • ERβ
  • MAPK
  • NF-κB