PMID- 30774633
OWN - NLM
STAT- MEDLINE
DCOM- 20191231
LR  - 20200309
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Deficiency in IL-33/ST2 Axis Reshapes Mitochondrial Metabolism in 
      Lipopolysaccharide-Stimulated Macrophages.
PG  - 127
LID - 10.3389/fimmu.2019.00127 [doi]
LID - 127
AB  - The polarization and function of macrophages play essential roles in controlling 
      immune responses. Interleukin (IL)-33 is a member of the IL-1 family that has 
      been shown to influence macrophage activation and polarization, but the 
      underlying mechanisms are not fully understood. Mitochondrial metabolism has been 
      reported to be a central player in shaping macrophage polarization; previous 
      studies have shown that both aerobic glycolysis and oxidative phosphorylation 
      uniquely regulate the functions of M1 and M2 macrophages. Whether IL-33 polarizes 
      macrophages by reshaping mitochondrial metabolism requires further investigation. 
      In this work, we examined the mitochondrial metabolism of bone marrow-derived 
      macrophages (BMDMs) from either wild type (WT), Il33-overexpressing, or IL-33 
      receptor knockout (St2(-/-)) mice challenged with lipopolysaccharide (LPS). We 
      found that after LPS stimulation, compared with WT BMDMs, St2(-/-) BMDMs had 
      reduced cytokine production and increased numbers and activity of mitochondria 
      via the metabolism regulator peroxisome proliferator-activated receptor-C 
      coactivator-1 alpha (PGC1alpha). This was demonstrated by increased mitochondrial DNA 
      copy number, mitochondria counts, mitochondria fission- and fusion-related gene 
      expression, oxygen consumption rates, and ATP production, and decreased glucose 
      uptake, lactate production, and extracellular acidification rates. For 
      Il33-overexpressing BMDMs, the metabolic reprogramming upon LPS stimulation was 
      similar to WT BMDMs, and was accompanied by increased M1 macrophage activity. Our 
      findings suggested that the pleiotropic IL-33/ST2 pathway may influence the 
      polarization and function of macrophages by regulating mitochondrial metabolism.
FAU - Xu, Huadan
AU  - Xu H
AD  - Key Laboratory of Pathobiology, Ministry of Education, Department of 
      Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 
      China.
FAU - Sun, Liankun
AU  - Sun L
AD  - Key Laboratory of Pathobiology, Ministry of Education, Department of 
      Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 
      China.
FAU - He, Yichun
AU  - He Y
AD  - Department of Neurosurgery, China-Japan Union Hospital, Jilin University, 
      Changchun, China.
FAU - Yuan, Xiaofeng
AU  - Yuan X
AD  - Department of Pediatrics, Affiliated Hospital of Changchun University of Chinese 
      Medicine, Changchun, China.
FAU - Niu, Junqi
AU  - Niu J
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Su, Jing
AU  - Su J
AD  - Key Laboratory of Pathobiology, Ministry of Education, Department of 
      Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 
      China.
FAU - Li, Dong
AU  - Li D
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun, 
      China.
AD  - Department of Immunology, College of Basic Medical Sciences, Jilin University, 
      Changchun, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190201
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Il1rl1 protein, mouse)
RN  - 0 (Interleukin-1 Receptor-Like 1 Protein)
RN  - 0 (Interleukin-33)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - DNA, Mitochondrial/genetics
MH  - Interleukin-1 Receptor-Like 1 Protein/*genetics/metabolism
MH  - Interleukin-33/*genetics/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Mitochondria/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Signal Transduction
PMC - PMC6367255
OTO - NOTNLM
OT  - ATP
OT  - IL-33
OT  - PGC1alpha
OT  - ST2
OT  - macrophage
EDAT- 2019/02/19 06:00
MHDA- 2020/01/01 06:00
PMCR- 2019/01/01
CRDT- 2019/02/19 06:00
PHST- 2018/05/22 00:00 [received]
PHST- 2019/01/15 00:00 [accepted]
PHST- 2019/02/19 06:00 [entrez]
PHST- 2019/02/19 06:00 [pubmed]
PHST- 2020/01/01 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00127 [doi]
PST - epublish
SO  - Front Immunol. 2019 Feb 1;10:127. doi: 10.3389/fimmu.2019.00127. eCollection 
      2019.