PMID- 24792436 OWN - NLM STAT- MEDLINE DCOM- 20140820 LR - 20211021 IS - 1873-2968 (Electronic) IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 90 IP - 1 DP - 2014 Jul 1 TI - Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-kappaB activation. PG - 73-87 LID - S0006-2952(14)00239-1 [pii] LID - 10.1016/j.bcp.2014.04.015 [doi] AB - Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1beta, PGE2, TNF-alpha and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IkappaBalpha phosphorylation and degradation, and blocked the NF-kappaB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-kappaB activation. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zhao, Zhanzhong AU - Zhao Z AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China; Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: zhao.xinghui@gmail.com. FAU - Tang, Xiangfang AU - Tang X AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: xiangfangtang@163.com. FAU - Zhao, Xinghui AU - Zhao X AD - Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: zhanzhongzhao@hotmail.com. FAU - Zhang, Minhong AU - Zhang M AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: zhangminhong@caas.cn. FAU - Zhang, Weijian AU - Zhang W AD - Shanghai Municipal Animal Innocuous Treatment Center, No. 50 Lane 4088, Puwei Road, Fengxian District, Shanghai 201415, People's Republic of China. Electronic address: zhang_clxz@163.com. FAU - Hou, Shaohua AU - Hou S AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: houshaohua@caas.cn. FAU - Yuan, Weifeng AU - Yuan W AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: yuanweifeng@caas.cn. FAU - Zhang, Hongfu AU - Zhang H AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: zhanghongfu@caas.cn. FAU - Shi, Lijun AU - Shi L AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: shilijun@caas.cn. FAU - Jia, Hong AU - Jia H AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: jiahong@caas.cn. FAU - Liang, Lin AU - Liang L AD - State Key Laboratory of Animal Nutrition, Department of Veterinary Medicine, Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China. Electronic address: lianglin1020@gmail.com. FAU - Lai, Zhi AU - Lai Z AD - Biopharmavet Institute, No.161 Zhenye Road, Songjiang District, Shanghai 201619, People's Republic of China. Electronic address: zhilai@263.net. FAU - Gao, Junfeng AU - Gao J AD - Biopharmavet Institute, No.161 Zhenye Road, Songjiang District, Shanghai 201619, People's Republic of China. Electronic address: junfenggao3004@yahoo.com.cn. FAU - Zhang, Keyu AU - Zhang K AD - Key Laboratory for Veterinary Drug Safety Evaluation and Residue Research, Department of Pharmacy, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 518 Ziyue Road, Minhang District, Shanghai 200241, People's Republic of China. Electronic address: zcole202@yahoo.com.cn. FAU - Fu, Ling AU - Fu L AD - Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: fuling610624@qq.com. FAU - Chen, Wei AU - Chen W AD - Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: cw789661@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140430 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 9T02S42WQO (tylvalosin) RN - YEF4JXN031 (Tylosin) SB - IM MH - Acute Lung Injury/metabolism/*prevention & control MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Blotting, Western MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cell Line MH - Chemical and Drug Induced Liver Injury/metabolism/prevention & control MH - Cytokines/metabolism MH - *Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Inflammation Mediators/metabolism MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred ICR MH - NF-kappa B/*metabolism MH - Porcine Reproductive and Respiratory Syndrome/physiopathology/prevention & control/virology MH - Porcine respiratory and reproductive syndrome virus/physiology MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - Swine MH - Tylosin/*analogs & derivatives/pharmacology MH - Weight Gain/drug effects PMC - PMC7092911 OTO - NOTNLM OT - Acute lung injury OT - Anti-inflammation OT - NF-kappaB OT - Tylvalosin EDAT- 2014/05/06 06:00 MHDA- 2014/08/21 06:00 PMCR- 2014/04/30 CRDT- 2014/05/06 06:00 PHST- 2014/03/12 00:00 [received] PHST- 2014/04/21 00:00 [revised] PHST- 2014/04/22 00:00 [accepted] PHST- 2014/05/06 06:00 [entrez] PHST- 2014/05/06 06:00 [pubmed] PHST- 2014/08/21 06:00 [medline] PHST- 2014/04/30 00:00 [pmc-release] AID - S0006-2952(14)00239-1 [pii] AID - 10.1016/j.bcp.2014.04.015 [doi] PST - ppublish SO - Biochem Pharmacol. 2014 Jul 1;90(1):73-87. doi: 10.1016/j.bcp.2014.04.015. Epub 2014 Apr 30.