PMID- 30958608
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 43
IP  - 6
DP  - 2019 Jun
TI  - Dexmedetomidine protects against high mobility group box 1-induced cellular 
      injury by inhibiting pyroptosis.
PG  - 651-657
LID - 10.1002/cbin.11140 [doi]
AB  - Dexmedetomidine (DEX) is a widely used clinical anesthetic with proven 
      anti-inflammatory effects. Both high mobility group box 1 (HMGB1) and pyroptosis 
      play an important role in the inflammatory response to infection and trauma. Thus 
      far, there have been no studies published addressing the effect of DEX on HMGB1 
      and pyroptosis. In order to fill this gap in the literature, bone marrow-derived 
      macrophages (BMDMs) were exposed to HMGB1 (4 microg/mL) with or without DEX (50 muM) 
      pretreatment. The production of pro-inflammatory cytokines [such as tumor 
      necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-18], phosphorylation of 
      extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and P38, and the 
      activation of caspase-1 were measured by enzyme immunosorbent assay, western blot 
      analysis, confocal microscope, and flow cytometry, respectively. We found that 
      DEX protected against HMGB1-induced cell death of BMDMs. In addition, DEX 
      suppressed the generation of TNF-alpha, IL-1beta, and IL-18 as well as the 
      phosphorylation of ERK1/2 and P38. Moreover, DEX inhibited caspase-1 activation 
      and decreased pyroptosis. Taken together, these findings demonstrate the 
      protective effect of DEX in mediating HMGB1-induced cellular injury, thus 
      indicating that DEX may be a potential therapeutic candidate for the management 
      of infection and trauma-derived inflammation.
CI  - (c) 2019 International Federation for Cell Biology.
FAU - Ji, Xuexia
AU  - Ji X
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Guo, Yuanbo
AU  - Guo Y
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Zhou, Guobin
AU  - Zhou G
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Science and Education, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Zhang, Jianxing
AU  - Zhang J
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Wang, Zhipeng
AU  - Wang Z
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
FAU - Wang, Qing
AU  - Wang Q
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, 510080, Guangzhou, China.
LA  - eng
GR  - 2011B031800149/Guangdong Province Science and Technology Project/
PT  - Journal Article
DEP - 20190425
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Dexmedetomidine/*pharmacology
MH  - HMGB1 Protein/metabolism/*pharmacology
MH  - Inflammation/metabolism/pathology
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - MAP Kinase Signaling System
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pyroptosis/*drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/drug effects/metabolism
OTO - NOTNLM
OT  - caspase-1
OT  - dexmedetomidine
OT  - high mobility group box 1
OT  - pyroptosis
EDAT- 2019/04/09 06:00
MHDA- 2019/09/10 06:00
CRDT- 2019/04/09 06:00
PHST- 2018/11/07 00:00 [received]
PHST- 2019/03/23 00:00 [accepted]
PHST- 2019/04/09 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2019/04/09 06:00 [entrez]
AID - 10.1002/cbin.11140 [doi]
PST - ppublish
SO  - Cell Biol Int. 2019 Jun;43(6):651-657. doi: 10.1002/cbin.11140. Epub 2019 Apr 25.