1. Florfenicol alleviated lipopolysaccharide (LPS)-induced inflammatory responses in Ctenopharyngodon idella through inhibiting toll / NF-κB signaling pathways
- Author
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Shaodong Zeng, Pei Li, Chunliang Yang, and Jianzhi Ye
- Subjects
Lipopolysaccharides ,0301 basic medicine ,Carps ,Lipopolysaccharide ,Anti-Inflammatory Agents ,Aquatic Science ,Pharmacology ,Proinflammatory cytokine ,Nitric oxide ,Fish Diseases ,Random Allocation ,03 medical and health sciences ,chemistry.chemical_compound ,Animals ,Environmental Chemistry ,Inflammation ,Thiamphenicol ,Dose-Response Relationship, Drug ,biology ,Toll-Like Receptors ,NF-kappa B ,04 agricultural and veterinary sciences ,General Medicine ,IRAK4 ,Nitric oxide synthase ,IκBα ,030104 developmental biology ,chemistry ,040102 fisheries ,TLR4 ,biology.protein ,0401 agriculture, forestry, and fisheries ,Tumor necrosis factor alpha ,Signal Transduction - Abstract
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 μg/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-α, IL-6 and IL-1β, 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-κBα (IκBα) 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-α, IL-6 and IL-1β, 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-α, IL-6, IL-1β, 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-κB) p65 and degradation inhibitor of IκBα. 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-1β, and TNF-α expressions through the down-regulation of Toll/NF-κB signaling pathways.
- Published
- 2019
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