title: Involvement of mitogen-activated protein kinase and NF-κB signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells.
abstract: 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-κB 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-κB signaling pathways with its subsequent influence on proinflammatory action.
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Jingying
authors: J
authors: Zhu
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Wenyi
authors: W
authors: Qian
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Yixin
authors: Y
authors: Wang
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Rong
authors: R
authors: Gao
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Jun
authors: J
authors: Wang
authors: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Hang
authors: H
authors: Xiao
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D015854:Up-Regulation
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D015850:Interleukin-6; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C076994:perfluorooctane sulfonic acid
keywords: MAPK; NF-κB; PFOS; immunomodulatory cytokines; microglia