PMID- 32634441
OWN - NLM
STAT- MEDLINE
DCOM- 20210518
LR  - 20240329
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 883
DP  - 2020 Sep 15
TI  - Modulation of LPS-induced inflammatory cytokine production by a novel glycogen 
      synthase kinase-3 inhibitor.
PG  - 173340
LID - S0014-2999(20)30432-5 [pii]
LID - 10.1016/j.ejphar.2020.173340 [doi]
AB  - Sepsis is a serious condition that can lead to long-term organ damage and death. 
      At the molecular level, the hallmark of sepsis is the elevated expression of a 
      multitude of potent cytokines, i.e. a cytokine storm. For sepsis involving 
      gram-negative bacteria, macrophages recognize lipopolysaccharide (LPS) shed from 
      the bacteria, activating Toll-like-receptor 4 (TLR4), and triggering a cytokine 
      storm. Glycogen synthase kinase-3 (GSK-3) is a highly active kinase that has been 
      implicated in LPS-induced cytokine production. Thus, compounds that inhibit GSK-3 
      could be potential therapeutics for sepsis. Our group has recently described a 
      novel and highly selective inhibitor of GSK-3 termed COB-187. In the present 
      study, using THP-1 macrophages, we evaluated the ability of COB-187 to attenuate 
      LPS-induced cytokine production. We found that COB-187 significantly reduced, at 
      the protein and mRNA levels, cytokines induced by LPS (e.g. IL-6, TNF-alpha, IL-1beta, 
      CXCL10, and IFN-beta). Further, the data suggest that the inhibition could be due, 
      at least in part, to COB-187 reducing NF-kappaB (p65/p50) DNA binding activity as 
      well as reducing IRF-3 phosphorylation at Serine 396. Thus, COB-187 appears to be 
      a potent inhibitor of the cytokine storm induced by LPS.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Noori, Mahboubeh S
AU  - Noori MS
AD  - Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH, 
      45701, USA. Electronic address: mn559814@ohio.edu.
FAU - Courreges, Maria C
AU  - Courreges MC
AD  - Department of Specialty Medicine, Ohio University, Athens, OH, 45701, USA.
FAU - Bergmeier, Stephen C
AU  - Bergmeier SC
AD  - Biomedical Engineering Program, Ohio University, Athens, OH, 45701, USA; 
      Department of Chemistry and Biochemistry, Ohio University, Athens, OH, 45701, 
      USA.
FAU - McCall, Kelly D
AU  - McCall KD
AD  - Department of Specialty Medicine, Ohio University, Athens, OH, 45701, USA; 
      Biomedical Engineering Program, Ohio University, Athens, OH, 45701, USA; The 
      Diabetes Institute, Ohio University, Athens, OH, 45701, USA; Molecular and 
      Cellular Biology Program, Ohio University, Athens, OH, 45701, USA; Translational 
      Biomedical Science Program, Ohio University, Athens, OH, 45701, USA.
FAU - Goetz, Douglas J
AU  - Goetz DJ
AD  - Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH, 
      45701, USA; Biomedical Engineering Program, Ohio University, Athens, OH, 45701, 
      USA. Electronic address: goetzd@ohio.edu.
LA  - eng
GR  - R15 GM110602/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20200704
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (IRF3 protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cytokine Release Syndrome/chemically induced/enzymology/genetics/*prevention & 
      control
MH  - Cytokines/genetics/*metabolism
MH  - Down-Regulation
MH  - Glycogen Synthase Kinase 3/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/*drug effects/enzymology
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Sepsis/chemically induced/enzymology/genetics/prevention & control
MH  - Signal Transduction
MH  - THP-1 Cells
PMC - PMC7334664
OTO - NOTNLM
OT  - COB-187
OT  - Cytokine
OT  - Glycogen synthase kinase-3
OT  - NF-kappaB
OT  - Sepsis
EDAT- 2020/07/08 06:00
MHDA- 2021/05/19 06:00
PMCR- 2020/07/04
CRDT- 2020/07/08 06:00
PHST- 2020/04/08 00:00 [received]
PHST- 2020/06/28 00:00 [revised]
PHST- 2020/06/29 00:00 [accepted]
PHST- 2020/07/08 06:00 [pubmed]
PHST- 2021/05/19 06:00 [medline]
PHST- 2020/07/08 06:00 [entrez]
PHST- 2020/07/04 00:00 [pmc-release]
AID - S0014-2999(20)30432-5 [pii]
AID - 173340 [pii]
AID - 10.1016/j.ejphar.2020.173340 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2020 Sep 15;883:173340. doi: 10.1016/j.ejphar.2020.173340. Epub 
      2020 Jul 4.