PMID- 30062462 OWN - NLM STAT- MEDLINE DCOM- 20190722 LR - 20190722 IS - 1559-0720 (Electronic) IS - 0163-4984 (Linking) VI - 189 IP - 1 DP - 2019 May TI - Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-kappaB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver. PG - 157-171 LID - 10.1007/s12011-018-1458-z [doi] AB - 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-kappaB) signaling pathway by increasing (p < 0.01 or p < 0.05) the production of NF-kappaB and inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-beta) and reducing (p < 0.01 or p < 0.05) the production of the inhibitory kappa B (IkappaB). 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-1beta (IL-1beta), 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-kappaB 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-beta). FAU - Chen, Linlin AU - Chen L AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. FAU - Kuang, Ping AU - Kuang P AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. FAU - Liu, Huan AU - Liu H AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. FAU - Wei, Qin AU - Wei Q AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. FAU - Cui, Hengmin AU - Cui H AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. cui580420@sicau.edu.cn. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. cui580420@sicau.edu.cn. AD - Key Laboratory of Agricultural Information Engineering of Sichuan Province, Sichuan Agriculture University, Ya'an, 625014, Sichuan, China. cui580420@sicau.edu.cn. FAU - Fang, Jing AU - Fang J AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. FAU - Zuo, Zhicai AU - Zuo Z AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. FAU - Deng, Junliang AU - Deng J AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. FAU - Li, Yinglun AU - Li Y AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. FAU - Wang, Xun AU - Wang X AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. FAU - Zhao, Ling AU - Zhao L AD - College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China. AD - Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China. LA - eng GR - IRT 0848/The program for Changjiang scholars and innovative research team in university/ GR - 03572437; 03571800/The Shuangzhi Project of Sichuan Agricultural University/ PT - Journal Article DEP - 20180730 PL - United States TA - Biol Trace Elem Res JT - Biological trace element research JID - 7911509 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 8ZYQ1474W7 (Sodium Fluoride) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cytokines/*metabolism MH - Inflammation/*chemically induced/*metabolism MH - Liver/*drug effects/*metabolism MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-kappa B/*metabolism MH - Random Allocation MH - Signal Transduction/drug effects MH - Sodium Fluoride/*pharmacology OTO - NOTNLM OT - Inflammatory responses OT - Liver OT - MAPK OT - NF-kappaB OT - Sodium fluoride EDAT- 2018/08/01 06:00 MHDA- 2019/07/23 06:00 CRDT- 2018/08/01 06:00 PHST- 2018/05/15 00:00 [received] PHST- 2018/07/20 00:00 [accepted] PHST- 2018/08/01 06:00 [pubmed] PHST- 2019/07/23 06:00 [medline] PHST- 2018/08/01 06:00 [entrez] AID - 10.1007/s12011-018-1458-z [pii] AID - 10.1007/s12011-018-1458-z [doi] PST - ppublish SO - Biol Trace Elem Res. 2019 May;189(1):157-171. doi: 10.1007/s12011-018-1458-z. Epub 2018 Jul 30.