PMID- 33029757
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 44
IP  - 2
DP  - 2021 Apr
TI  - Dimethyl Itaconate Alleviates the Inflammatory Responses of Macrophages in 
      Sepsis.
PG  - 549-557
LID - 10.1007/s10753-020-01352-4 [doi]
AB  - Sepsis is an inflammatory disease characterized by dysregulation of inflammation. 
      Macrophage-mediated inflammation has been implicated in the pathophysiology of 
      sepsis. Itaconate is a metabolite produced in activated macrophages which has 
      anti-inflammatory activities. In the present study, we investigated the potential 
      effects of a cell-permeable itaconate derivative dimethyl itaconate on 
      inflammation in sepsis. We established a lipopolysaccharide (LPS)-induced septic 
      mouse model and administered dimethyl itaconate to the septic mice. The survival 
      rate, serum level of pro-inflammatory cytokines, and lung pathology were 
      evaluated. We also administered dimethyl itaconate to LPS-treated bone 
      marrow-derived macrophages (BMDMs), and measured the cytokine production and Nrf2 
      expression. We also evaluated the effects of dimethyl itaconate on Nrf2-deficient 
      mice. Administration of dimethyl itaconate enhanced survival rate, decreased 
      serum level of TNF-alpha and IL-6, and ameliorated lung injury in septic mice. 
      Dimethyl itaconate also suppressed LPS-induced production of TNF-alpha, IL-6, and 
      NOS2 in BMDMs. Dimethyl itaconate activated Nrf2 and promoted the expression of 
      Nrf2 and its downstream factor HO-1 and NQO-1. The regulatory activities of 
      dimethyl itaconate on inflammatory cytokine production, mouse survival rate were 
      abolished in septic Nrf2(-/-) mice. Dimethyl itaconate suppressed the 
      inflammatory responses of macrophages in sepsis.
FAU - Zhang, Sheng
AU  - Zhang S
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Jiao, Yalou
AU  - Jiao Y
AD  - Department of Reproductive Medicine, Xingtai People's Hospital of Hebei Province, 
      No. 16 Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Li, Chao
AU  - Li C
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Liang, Xiao
AU  - Liang X
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Jia, Huiqin
AU  - Jia H
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Nie, Zhelong
AU  - Nie Z
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China.
FAU - Zhang, Yanwei
AU  - Zhang Y
AUID- ORCID: 0000-0001-5718-8831
AD  - Department of Emergency, Xingtai People's Hospital of Hebei Province, No. 16 
      Hongxing Street, Xingtai, 054031, Hebei, China. 0210130024@163.com.
LA  - eng
PT  - Journal Article
DEP - 20201007
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Succinates)
RN  - 11JIB0YI93 (dimethyl itaconate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Biomarkers/blood
MH  - Blotting, Western
MH  - Cytokines/blood
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Inflammation/blood/*drug therapy/etiology/immunology
MH  - Lipopolysaccharides
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Random Allocation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sepsis/blood/*drug therapy/etiology/immunology
MH  - Succinates/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - dimethyl itaconate
OT  - inflammation
OT  - macrophages
OT  - sepsis
EDAT- 2020/10/09 06:00
MHDA- 2021/11/10 06:00
CRDT- 2020/10/08 05:35
PHST- 2020/06/18 00:00 [received]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/09/17 00:00 [revised]
PHST- 2020/10/09 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2020/10/08 05:35 [entrez]
AID - 10.1007/s10753-020-01352-4 [pii]
AID - 10.1007/s10753-020-01352-4 [doi]
PST - ppublish
SO  - Inflammation. 2021 Apr;44(2):549-557. doi: 10.1007/s10753-020-01352-4. Epub 2020 
      Oct 7.