PMID- 31472264 OWN - NLM STAT- MEDLINE DCOM- 20200207 LR - 20200207 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 94 DP - 2019 Nov TI - Florfenicol alleviated lipopolysaccharide (LPS)-induced inflammatory responses in Ctenopharyngodon idella through inhibiting toll / NF-kappaB signaling pathways. PG - 479-484 LID - S1050-4648(19)30873-3 [pii] LID - 10.1016/j.fsi.2019.08.073 [doi] AB - The present study was conducted to evaluate the anti-inflammatory activity of florfenicol (FFC) against lipopolysaccharide (LPS)-induced inflammatory responses in Ctenopharyngodon idella in vivo and in vitro. Head-kidney (HK) macrophages were pre-treated with 10 mug/mL LPS and then exposed to different concentrations of FFC to determine its in vitro anti-inflammatory activity. Inhibitory effect of FFC on inflammatory mediators TNF-alpha, IL-6 and IL-1beta, as well as LPS-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were assayed by ELISA. The expression level of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were investigated by RT-PCR. Expression level of TLR-related genes (TLR1, TLR2, TLR4, TLR7, TLR8) expression, tumor necrosis factor receptor-associated factor 6 (TRAF6), transforming growth factor-b-activated kinase 1 (TAK1), Myeloid differentiation factor 88 (MyD88), nucleus p65, NF-kappaBalpha (IkappaBalpha) were measured by RT-PCR after grass carp were treated with 50, 100 and 200 mg FFC/kg body weight for 3 days. Results from in vitro tests demonstrated that FFC dose-dependently inhibited LPS-induced inflammatory cytokines TNF-alpha, IL-6 and IL-1beta, inflammatory factors NO and PGE 2 production in macrophages. In addition, iNOS and COX-2 expression levels decreased significantly as compared with LPS treated group. In vivo test demonstrated that treatment with FFC prevented the LPS-induced upregulation of TNF-alpha, IL-6, IL-1beta, NO and PGE 2. The expression level of iNOS, and COX-2 in FFC-treated grass carp were also downregulated as compared with LPS treated fish. Besides, FFC blocked the expression of Toll-like receptor 2 (TLR2) and then suppressed the phosphorylation of nuclear transcription factor-kappa B (NF-kappaB) p65 and degradation inhibitor of IkappaBalpha. Furthermore, administration of FFC inhibited the up-regulation of IRAK4, TRAF6 and TAK1 induced by LPS. These results suggest that the anti-inflammatory properties of FFC might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1beta, and TNF-alpha expressions through the down-regulation of Toll/NF-kappaB signaling pathways. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Li, Pei AU - Li P AD - Center for Food Quality Supervision and Testing (Zhanjiang)Ministry of Agriculture and Rural Affairs PR China, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang, 52400, China; Institute for Fisheries Sciences, Guangxi University, Nanning, 53000, China. FAU - Ye, Jianzhi AU - Ye J AD - Center for Food Quality Supervision and Testing (Zhanjiang)Ministry of Agriculture and Rural Affairs PR China, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang, 52400, China. FAU - Zeng, Shaodong AU - Zeng S AD - Center for Food Quality Supervision and Testing (Zhanjiang)Ministry of Agriculture and Rural Affairs PR China, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang, 52400, China. FAU - Yang, Chunliang AU - Yang C AD - Center for Food Quality Supervision and Testing (Zhanjiang)Ministry of Agriculture and Rural Affairs PR China, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang, 52400, China. Electronic address: 3403009643@qq.com. LA - eng PT - Journal Article DEP - 20190828 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptors) RN - 9J97307Y1H (florfenicol) RN - FLQ7571NPM (Thiamphenicol) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Carps/genetics/*immunology MH - Dose-Response Relationship, Drug MH - Fish Diseases/chemically induced/*drug therapy MH - Inflammation/chemically induced/drug therapy/*veterinary MH - Lipopolysaccharides/pharmacology MH - NF-kappa B/physiology MH - Random Allocation MH - Signal Transduction/drug effects/physiology MH - Thiamphenicol/*analogs & derivatives/pharmacology MH - Toll-Like Receptors/physiology OTO - NOTNLM OT - Ctenopharyngodon idella OT - Florfenicol OT - Inflammatory responses OT - Toll/NF-kappaB signaling pathways OT - lipopolysaccharide EDAT- 2019/09/01 06:00 MHDA- 2020/02/08 06:00 CRDT- 2019/09/01 06:00 PHST- 2019/06/26 00:00 [received] PHST- 2019/08/25 00:00 [revised] PHST- 2019/08/27 00:00 [accepted] PHST- 2019/09/01 06:00 [pubmed] PHST- 2020/02/08 06:00 [medline] PHST- 2019/09/01 06:00 [entrez] AID - S1050-4648(19)30873-3 [pii] AID - 10.1016/j.fsi.2019.08.073 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2019 Nov;94:479-484. doi: 10.1016/j.fsi.2019.08.073. Epub 2019 Aug 28.