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Int. J. Mol. Sci. 2014, 15(7), 12119-12134; doi:10.3390/ijms150712119

Cordycepin Inhibits Lipopolysaccharide (LPS)-Induced Tumor Necrosis Factor (TNF)-α Production via Activating AMP-Activated Protein Kinase (AMPK) Signaling

1
Department of Respiration, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China
2
Department of Pediatrics, the First People's Hospital of Hangzhou, Hangzhou 310003, China
3
Department of Pediatrics, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China
*
Author to whom correspondence should be addressed.
Received: 19 April 2014 / Revised: 6 June 2014 / Accepted: 18 June 2014 / Published: 8 July 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Tumor necrosis factor (TNF)-α is elevated during the acute phase of Kawasaki disease (KD), which damages vascular endothelial cells to cause systemic vasculitis. In the current study, we investigated the potential role of cordycepin on TNFα expression in both lipopolysaccharide (LPS)-stimulated macrophages and ex vivo cultured peripheral blood mononuclear cells (PBMCs) of KD patients. We found that cordycepin significantly suppressed LPS-induced TNFα expression and production in mouse macrophages (RAW 264.7 cells and bone marrow-derived macrophages (BMDMs)). Meanwhile, cordycepin alleviated TNFα production in KD patients’ PBMCs. PBMCs from healthy controls had a much lower level of basal TNF-α content than that of KD patients. LPS-induced TNF-α production in healthy controls’ PBMCs was also inhibited by cordycepin. For the mechanism study, we discovered that cordycepin activated AMP-activated protein kinase (AMPK) signaling in both KD patients’ PBMCs and LPS-stimulated macrophages, which mediated cordycepin-induced inhibition against TNFα production. AMPK inhibition by its inhibitor (compound C) or by siRNA depletion alleviated cordycepin’s effect on TNFα production. Further, we found that cordycepin inhibited reactive oxygen species (ROS) production and nuclear factor kappa B (NF-κB) activation in LPS-stimulate RAW 264.7 cells or healthy controls’ PBMCs. PBMCs of KD patients showed higher basal level of ROS and NF-κB activation, which was also inhibited by cordycepin co-treatment. In conclusion, our data showed that cordycepin inhibited TNFα production, which was associated with AMPK activation as well as ROS and NF-κB inhibition. The results of this study should have significant translational relevance in managing this devastating disease. View Full-Text
Keywords: Kawasaki disease; cordycepin; TNFα (tumor necrosis factor α); AMPK (AMP-activated protein kinase); LPS (lipopolysaccharide) Kawasaki disease; cordycepin; TNFα (tumor necrosis factor α); AMPK (AMP-activated protein kinase); LPS (lipopolysaccharide)
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MDPI and ACS Style

Zhang, J.-L.; Xu, Y.; Shen, J. Cordycepin Inhibits Lipopolysaccharide (LPS)-Induced Tumor Necrosis Factor (TNF)-α Production via Activating AMP-Activated Protein Kinase (AMPK) Signaling. Int. J. Mol. Sci. 2014, 15, 12119-12134.

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