4.5 Article

Involvement of mitogen-activated protein kinase and NF-B signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells

Journal

JOURNAL OF APPLIED TOXICOLOGY
Volume 35, Issue 12, Pages 1539-1549

Publisher

WILEY
DOI: 10.1002/jat.3119

Keywords

PFOS; immunomodulatory cytokines; MAPK; NF-kappa B; microglia

Categories

Funding

  1. National Natural Science Foundation of China [81273115, 81072329, 81473012, 81202230]
  2. Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
  3. Training and Innovation Program of Jiangsu Graduate [CXZZ13_0598]

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Microglial activation is closely related to the pathogenesis of neurodegenerative diseases by producing proinflammatory cytokines. Perfluorooctane sulfonic acid (PFOS), known as an emerging persistent organic pollutant, is reported to disturb human immune homeostasis; however, whether it affects cytokine production or the immune response in the central nervous system remains unclear. The present study was aimed to explore whether PFOS contributed to inflammatory action and to investigate the corresponding mechanisms in BV2 microglia. PFOS-mediated morphologic changes, cytokine responses and signaling events were examined by light microscopy, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot assays. Our results indicated that PFOS increased BV2 cells activation and simultaneously increased tumor necrosis factor alpha and interleukin-6 expression. In addition, the c-Jun N-terminal protein kinase inhibitor (SP600125), as well as ERK1/2 blocker (PD98059), transcriptionally at least, displayed anti-inflammatory properties on PFOS-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-B was specifically activated by PFOS as well. These results, taken together, suggested that PFOS exerts its functional effects on the response of microglial cell activation via, in part, the c-Jun N-terminal protein kinase, ERK and NF-B signaling pathways with its subsequent influence on proinflammatory action. Copyright (c) 2015 John Wiley & Sons, Ltd. Perfluorooctane sulfonic acid (PFOS) has been used in extensive commercial and industrial applications and is believed to be an emerging persistent organic pollutant. In this paper, we demonstrated that PFOS possesses immunomodulatory potential and exerts its action on inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6, in microglial cells. The inflammatory reaction mediated by PFOS was partially via mitogen-activated protein kinases (MAPK) and NF-B signals. Thus, these findings offer a potential mechanism for the study of proinflammatory activity of PFOS in the central nervous system.

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