title: Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride.
abstract: F toxicity to immune system, especially to macrophage, has been studied a lot recently. Nuclear factor-kappa B (NF-κB), as a transcription factor, plays a central role in immune and inflammatory responses via the regulation of downstream gene expression. Recent studies indicated that fluoride effect on inflammatory cytokine secretion, however, the molecular mechanism was less understood. In our study, peritoneal macrophages (PMs) were divided several groups and were administrated sodium fluoride (NaF, 50, 100, 200, 400, 800 μM) and/or lipopolysaccharide (LPS, 30 ng/mg). The mRNA expression of p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in macrophages exposed to fluoride was determined by quantitative real-time RT-PCR respectively. The translocation of NF-κB from cytoplasm to nucleus, which in a way reflects NF-κB activity, was demonstrated by Immunofluorescence and ELISA. Our results showed that fluoride had a dose-dependent effect on NF-κB activity, which coincided with LPS-induced mRNA expression of its downstream genes, iNOS and IL-1β. Fluoride alone causes no effect on gene expression. However, the mRNA expression of TNF-α showed non-NF-κB-dependent manner. Therefore, we come to the conclusion that fluoride can regulate LPS-induced mRNA expression of iNOS and IL-1β via NF-κB pathway in mouse peritoneal macrophages.
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, China.
authors.forename: Meijun
authors.initials: M
authors.lastname: Huo
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, China.
authors.forename: Guangsheng
authors.initials: G
authors.lastname: Li
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, China. Electronic address: wangjd53@outlook.com.
authors.forename: Jundong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005459:Fluorides / Q000633:toxicity*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D005459:Fluorides
keywords: Fluoride; Lipopolysaccharide; Macrophage; Nuclear factor-kappa B; Pro-inflammatory cytokine