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: Zhanzhong Zhao, Xiangfang Tang, Xinghui Zhao, Minhong Zhang, Weijian Zhang, Shaohua Hou, Weifeng Yuan, Hongfu Zhang, Lijun Shi, Hong Jia, Lin Liang, Zhi Lai, Junfeng Gao, Keyu Zhang, Ling Fu, Wei Chen
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 90 Issue 1 Pg. 73-87 (Jul 01 2014) ISSN: 1873-2968 [Electronic] England
• PMID: 24792436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Reactive Oxygen Species
• tylvalosin
• Tylosin

Topics

• Acute Lung Injury (metabolism, prevention & control)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Blotting, Western
• Bronchoalveolar Lavage Fluid (chemistry)
• Cell Line
• Chemical and Drug Induced Liver Injury (metabolism, prevention & control)
• Cytokines (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Female
• Inflammation Mediators (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Porcine Reproductive and Respiratory Syndrome (physiopathology, prevention & control, virology)
• Porcine respiratory and reproductive syndrome virus (physiology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Swine
• Tylosin (analogs & derivatives, pharmacology)
• Weight Gain (drug effects)