title: Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation.
abstract: 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-1β, PGE2, TNF-α 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 IκBα phosphorylation and degradation, and blocked the NF-κB 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-κB activation.
authors.affiliation: 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.
authors.forename: Zhanzhong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Xiangfang
authors.initials: X
authors.lastname: Tang
authors.affiliation: Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: zhanzhongzhao@hotmail.com.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Minhong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Weijian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Hou
authors.affiliation: 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.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lijun
authors.initials: L
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Liang
authors.affiliation: Biopharmavet Institute, No.161 Zhenye Road, Songjiang District, Shanghai 201619, People's Republic of China. Electronic address: zhilai@263.net.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Biopharmavet Institute, No.161 Zhenye Road, Songjiang District, Shanghai 201619, People's Republic of China. Electronic address: junfenggao3004@yahoo.com.cn.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Keyu
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: fuling610624@qq.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.affiliation: Beijing Institute of Biotechnology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People's Republic of China. Electronic address: cw789661@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D015645:Tylosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C545430:tylvalosin; D015645:Tylosin
keywords: Acute lung injury; Anti-inflammation; NF-κB; Tylvalosin