PMID- 25007068
OWN - NLM
STAT- MEDLINE
DCOM- 20150410
LR  - 20220316
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 15
IP  - 7
DP  - 2014 Jul 8
TI  - Cordycepin inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor 
      (TNF)-alpha production via activating amp-activated protein kinase (AMPK) signaling.
PG  - 12119-34
LID - 10.3390/ijms150712119 [doi]
AB  - Tumor necrosis factor (TNF)-alpha 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 TNFalpha 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 TNFalpha 
      expression and production in mouse macrophages (RAW 264.7 cells and bone 
      marrow-derived macrophages (BMDMs)). Meanwhile, cordycepin alleviated TNFalpha 
      production in KD patients' PBMCs. PBMCs from healthy controls had a much lower 
      level of basal TNF-alpha content than that of KD patients. LPS-induced TNF-alpha 
      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 TNFalpha 
      production. AMPK inhibition by its inhibitor (compound C) or by siRNA depletion 
      alleviated cordycepin's effect on TNFalpha production. Further, we found that 
      cordycepin inhibited reactive oxygen species (ROS) production and nuclear factor 
      kappa B (NF-kappaB) activation in LPS-stimulate RAW 264.7 cells or healthy controls' 
      PBMCs. PBMCs of KD patients showed higher basal level of ROS and NF-kappaB 
      activation, which was also inhibited by cordycepin co-treatment. In conclusion, 
      our data showed that cordycepin inhibited TNFalpha production, which was associated 
      with AMPK activation as well as ROS and NF-kappaB inhibition. The results of this 
      study should have significant translational relevance in managing this 
      devastating disease.
FAU - Zhang, Jian-Li
AU  - Zhang JL
AD  - Department of Respiration, the First Affiliated Hospital of Zhejiang University 
      School of Medicine, Hangzhou 310003, China. jianlizhangjj@163.com.
FAU - Xu, Ying
AU  - Xu Y
AD  - Department of Pediatrics, the First People's Hospital of Hangzhou, Hangzhou 
      310003, China. yingyingxuxu163@163.com.
FAU - Shen, Jie
AU  - Shen J
AD  - Department of Pediatrics, the First Affiliated Hospital of Zhejiang University 
      School of Medicine, Hangzhou 310003, China. drchunlinwang@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140708
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Deoxyadenosines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - GZ8VF4M2J8 (cordycepin)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Case-Control Studies
MH  - Cell Culture Techniques
MH  - Cells, Cultured
MH  - Deoxyadenosines/*pharmacology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects/*metabolism
MH  - Mice
MH  - Mucocutaneous Lymph Node Syndrome/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC4139833
EDAT- 2014/07/10 06:00
MHDA- 2015/04/11 06:00
PMCR- 2014/07/01
CRDT- 2014/07/10 06:00
PHST- 2014/04/19 00:00 [received]
PHST- 2014/06/06 00:00 [revised]
PHST- 2014/06/18 00:00 [accepted]
PHST- 2014/07/10 06:00 [entrez]
PHST- 2014/07/10 06:00 [pubmed]
PHST- 2015/04/11 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - ijms150712119 [pii]
AID - ijms-15-12119 [pii]
AID - 10.3390/ijms150712119 [doi]
PST - epublish
SO  - Int J Mol Sci. 2014 Jul 8;15(7):12119-34. doi: 10.3390/ijms150712119.