Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-魏B activation

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• 作者：Zhanzhong Zhao^a ; ^b ; ¹ ; ^{zhao.xinghui@gmail.com" class="auth_mail} ; Xiangfang Tang^a ; ¹ ; ^{xiangfangtang@163.com" class="auth_mail} ; Xinghui Zhao^b ; ^{zhanzhongzhao@hotmail.com" class="auth_mail} ; Minhong Zhang^a ; ^{zhangminhong@caas.cn" class="auth_mail} ; Weijian Zhang^c ; ^{zhang_clxz@163.com" class="auth_mail} ; Shaohua Hou^a ; ^{houshaohua@caas.cn" class="auth_mail} ; Weifeng Yuan^a ; ^{yuanweifeng@caas.cn" class="auth_mail} ; Hongfu Zhang^a ; ^{zhanghongfu@caas.cn" class="auth_mail} ; Lijun Shi^a ; ^{shilijun@caas.cn" class="auth_mail} ; Hong Jia^a ; ^{jiahong@caas.cn" class="auth_mail} ; Lin Liang^a ; ^{lianglin1020@gmail.com" class="auth_mail} ; Zhi Lai^d ; ^{zhilai@263.net" class="auth_mail} ; Junfeng Gao^d ; ^{junfenggao3004@yahoo.com.cn" class="auth_mail} ; Keyu Zhang^e ; ^{zcole202@yahoo.com.cn" class="auth_mail} ; Ling Fu^b ; ^{fuling610624@qq.com" class="auth_mail} ; Wei Chen^b ; ^{cw789661@yahoo.com" class="auth_mail}
• 关键词：Tylvalosin ; Anti-inflammation ; Acute lung injury ; NF-魏B
• 刊名：Biochemical Pharmacology
• 出版年：1 July 2014
• 年：2014
• 卷：90
• 期：1
• 页码：73-87
• 全文大小：5520 K

文摘

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-1尾, PGE2, TNF-伪 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 I魏B伪 phosphorylation and degradation, and blocked the NF-魏B 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-魏B activation.