PMID- 30853417
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20200312
IS  - 2451-9448 (Electronic)
IS  - 2451-9448 (Linking)
VI  - 26
IP  - 5
DP  - 2019 May 16
TI  - Enhanced Cellular Polysulfides Negatively Regulate TLR4 Signaling and Mitigate 
      Lethal Endotoxin Shock.
PG  - 686-698.e4
LID - S2451-9456(19)30037-6 [pii]
LID - 10.1016/j.chembiol.2019.02.003 [doi]
AB  - Cysteine persulfide and cysteine polysulfides are cysteine derivatives having 
      sulfane sulfur atoms bound to cysteine thiol. Accumulating evidence has suggested 
      that cysteine persulfides/polysulfides are abundant in prokaryotes and eukaryotes 
      and play important roles in diverse biological processes such as antioxidant host 
      defense and redox-dependent signal transduction. Here, we show that enhancement 
      of cellular polysulfides by using polysulfide donors developed in this study 
      resulted in marked inhibition of lipopolysaccharide (LPS)-initiated macrophage 
      activation. Polysulfide donor treatment strongly suppressed LPS-induced 
      pro-inflammatory responses in macrophages by inhibiting Toll-like receptor 4 
      (TLR4) signaling. Other TLR signaling stimulants-including zymosan A-TLR2 and 
      poly(I:C)-TLR3-were also significantly suppressed by polysulfur donor treatment. 
      Administration of polysulfide donors protected mice from lethal endotoxin shock. 
      These data indicate that cellular polysulfides negatively regulate TLR4-mediated 
      pro-inflammatory signaling and hence constitute a potential target for 
      inflammatory disorders.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Zhang, Tianli
AU  - Zhang T
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Ono, Katsuhiko
AU  - Ono K
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Tsutsuki, Hiroyasu
AU  - Tsutsuki H
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Ihara, Hideshi
AU  - Ihara H
AD  - Department of Biological Science, Graduate School of Science, Osaka Prefecture 
      University, Osaka 599-8531, Japan.
FAU - Islam, Waliul
AU  - Islam W
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Akaike, Takaaki
AU  - Akaike T
AD  - Department of Environmental Medicine and Molecular Toxicology, Tohoku University 
      Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
FAU - Sawa, Tomohiro
AU  - Sawa T
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan. Electronic address: 
      sawat@kumamoto-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190307
PL  - United States
TA  - Cell Chem Biol
JT  - Cell chemical biology
JID - 101676030
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrites)
RN  - 0 (Sulfides)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 77238-31-4 (Interferon-beta)
RN  - 9080-49-3 (polysulfide)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Glutathione/chemistry
MH  - Immunity, Innate/drug effects
MH  - Interferon-beta/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/cytology/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitrites/metabolism
MH  - Phosphorylation/drug effects
MH  - RAW 264.7 Cells
MH  - Signal Transduction/*drug effects
MH  - Sulfides/chemical synthesis/*pharmacology
MH  - Toll-Like Receptor 4/chemistry/*metabolism
MH  - Tumor Necrosis Factor-alpha/blood
OTO - NOTNLM
OT  - cysteine persulfide
OT  - endotoxin shock
OT  - inflammation
OT  - innate immunity
OT  - metabolomics
OT  - polysulfide
OT  - signal transduction
OT  - sulfane sulfur
OT  - sulfur donor
OT  - toll-like receptors
EDAT- 2019/03/12 06:00
MHDA- 2020/03/13 06:00
CRDT- 2019/03/12 06:00
PHST- 2018/09/12 00:00 [received]
PHST- 2018/12/03 00:00 [revised]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/03/12 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/03/12 06:00 [entrez]
AID - S2451-9456(19)30037-6 [pii]
AID - 10.1016/j.chembiol.2019.02.003 [doi]
PST - ppublish
SO  - Cell Chem Biol. 2019 May 16;26(5):686-698.e4. doi: 
      10.1016/j.chembiol.2019.02.003. Epub 2019 Mar 7.