title: MAPK and NF-κB pathways are involved in bisphenol A-induced TNF-α and IL-6 production in BV2 microglial cells.
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.
authors.affiliation: 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.
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002460:Cell Line; D052244:Endocrine Disruptors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D004967:Estrogens / Q000031:analogs & derivatives / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D000077267:Fulvestrant; D007249:Inflammation / Q000188:drug therapy; D015850:Interleukin-6 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000098826:Bisphenol A Compounds
chemical_list: D000873:Anthracenes; D000893:Anti-Inflammatory Agents; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D065171:Estrogen Receptor Antagonists; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D000077267:Fulvestrant; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one