2. Academic Validation
  3. Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver

Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver

  • Biol Trace Elem Res. 2019 May;189(1):157-171. doi: 10.1007/s12011-018-1458-z.
Linlin Chen 1,  Ping Kuang 1,  Huan Liu 1,  Qin Wei 1,  Hengmin Cui 2 3 4,  Jing Fang 1 5,  Zhicai Zuo 1 5,  Junliang Deng 1 5,  Yinglun Li 1 5,  Xun Wang 1 5,  Ling Zhao 1 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China.
  • 2 College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. cui580420@sicau.edu.cn.
  • 3 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. cui580420@sicau.edu.cn.
  • 4 Key Laboratory of Agricultural Information Engineering of Sichuan Province, Sichuan Agriculture University, Ya'an, 625014, Sichuan, China. cui580420@sicau.edu.cn.
  • 5 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China.
PMID: 30062462 DOI: 10.1007/s12011-018-1458-z
Abstract

At present, no reports are focused on fluoride-induced hepatic inflammatory responses in human beings and Animals. This study aimed to investigate the mRNA and protein levels of inflammatory cytokines and signaling molecules for evaluating the effect of different doses (0, 12, 24, and 48 mg/kg) of sodium fluoride (NaF) on inflammatory reaction in the mouse liver by using methods of experimental pathology, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. We found that NaF in excess of 12 mg/kg caused the hepatic inflammatory responses, and the results showed that NaF activated the mitogen-activated protein kinases (MAPKs) signaling pathway by markedly increasing (p < 0.01 or p < 0.05) mRNA and protein levels of Apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated protein kinase kinases 1/2 (MEK1/2), extracellular signal-regulated protein kinases 1/2 (ERK1/2), mitogen-activated protein kinase kinases 4/7 (MEK4/7), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38) and mitogen-activated protein kinase kinases 3/6 (MEK3/6), and the nuclear factor-kappa B (NF-κB) signaling pathway by increasing (p < 0.01 or p < 0.05) the production of NF-κB and inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-β) and reducing (p < 0.01 or p < 0.05) the production of the inhibitory kappa B (IκB). Thus, NaF that caused the hepatic inflammatory responses was characterized by increasing (p < 0.01 or p < 0.05) the production of pro-inflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) via the activation of MAPKs and NF-κB pathways, and by significantly inhibiting (p < 0.01 or p < 0.05) the production of anti-inflammatory mediators including interleukin-4 (IL-4) and transforming growth factor beta (TGF-β).

Keywords

Inflammatory responses; Liver; MAPK; NF-κB; Sodium fluoride.

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