Resveratrol suppresses neutrophil activation via inhibition of Src family kinases to attenuate lung injury

Yung-Fong Tsai; Chun-Yu Chen; Wen-Yi Chang; Yu-Ting Syu; Tsong-Long Hwang

doi:10.1016/j.freeradbiomed.2019.09.021

Resveratrol suppresses neutrophil activation via inhibition of Src family kinases to attenuate lung injury

Free Radic Biol Med. 2019 Dec:145:67-77. doi: 10.1016/j.freeradbiomed.2019.09.021. Epub 2019 Sep 21.

Authors

Yung-Fong Tsai¹, Chun-Yu Chen¹, Wen-Yi Chang², Yu-Ting Syu², Tsong-Long Hwang³

Affiliations

¹ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.
² Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
³ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, 333, Taiwan; Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, 243, Taiwan. Electronic address: htl@mail.cgu.edu.tw.

PMID: 31550527
DOI: 10.1016/j.freeradbiomed.2019.09.021

Abstract

The natural stilbenoid, Resveratrol (RSV; 3,5,4'-trihydroxystilbene) has been shown to have beneficial effects on inflammatory diseases as well as cancer, neurodegenerative diseases, and cardiovascular disorders. The underlying mechanism by which RSV affects neutrophil activation has yet to be fully elucidated. In this study, we tested the hypothesis that RSV modulates the inflammatory activities of formyl-Met-Leu-Phe-stimulated human neutrophils. We employed a well-established isolated-neutrophil model to investigate the effects of RSV on neutrophil functions and the underlying mechanism of signaling transduction. The lipopolysaccharide-induced ALI murine model was employed to evaluate the therapeutic effects of RSV. Experiment results demonstrate that RSV reduces respiratory burst, degranulation, integrin expression, and cell adhesion in activated neutrophils in dose-dependent manners. RSV inhibited phosphorylation of Src family kinases (SFKs) and reduced their enzymatic activities. Moreover, RSV and a selective inhibitor of SFKs (PP2) reduced the phosphorylation of Bruton's tyrosine kinase and Vav. There results indicated that the inhibitory effects of RSV are mediated through the inhibition of the SFKs-Btk-Vav pathway. This study also revealed that RSV attenuates endotoxin-induced lung injury. We surmise that the therapeutic effects of RSV on ALI may derive from its anti-neutrophilic inflammation function and free radical-scavenging effects.

Keywords: Lung injury; Neutrophil; Reactive oxygen species; Resveratrol; Src family kinase; Superoxide anion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Lung Injury / chemically induced
Acute Lung Injury / drug therapy*
Acute Lung Injury / genetics
Acute Lung Injury / pathology
Agammaglobulinaemia Tyrosine Kinase / genetics
Animals
Humans
Lipopolysaccharides / toxicity
Mice
Neutrophil Activation / drug effects*
Neutrophil Activation / genetics
Neutrophils / drug effects
Phosphorylation
Resveratrol / pharmacology*
Signal Transduction / drug effects
src-Family Kinases / genetics*

Substances

Lipopolysaccharides
Agammaglobulinaemia Tyrosine Kinase
src-Family Kinases
Resveratrol