PMID- 31768073
OWN - NLM
STAT- MEDLINE
DCOM- 20200415
LR  - 20220418
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Jan
TI  - Endogenous oxidized phospholipids reprogram cellular metabolism and boost 
      hyperinflammation.
PG  - 42-53
LID - 10.1038/s41590-019-0539-2 [doi]
AB  - Pathogen-associated molecular patterns (PAMPs) have the capacity to couple 
      inflammatory gene expression to changes in macrophage metabolism, both of which 
      influence subsequent inflammatory activities. Similar to their microbial 
      counterparts, several self-encoded damage-associated molecular patterns (DAMPs) 
      induce inflammatory gene expression. However, whether this symmetry in host 
      responses between PAMPs and DAMPs extends to metabolic shifts is unclear. Here, 
      we report that the self-encoded oxidized phospholipid oxPAPC alters the 
      metabolism of macrophages exposed to lipopolysaccharide. While cells activated by 
      lipopolysaccharide rely exclusively on glycolysis, macrophages exposed to oxPAPC 
      also use mitochondrial respiration, feed the Krebs cycle with glutamine, and 
      favor the accumulation of oxaloacetate in the cytoplasm. This metabolite 
      potentiates interleukin-1beta production, resulting in hyperinflammation. Similar 
      metabolic adaptions occur in vivo in hypercholesterolemic mice and human 
      subjects. Drugs that interfere with oxPAPC-driven metabolic changes reduce 
      atherosclerotic plaque formation in mice, thereby underscoring the importance of 
      DAMP-mediated activities in pathophysiological conditions.
FAU - Di Gioia, Marco
AU  - Di Gioia M
AD  - Division of Immunology and Division of Gastroenterology, Boston Children's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Spreafico, Roberto
AU  - Spreafico R
AUID- ORCID: 0000-0001-8282-7658
AD  - Institute for Quantitative and Computational Biosciences, University of 
      California, Los Angeles, Los Angeles, CA, USA.
FAU - Springstead, James R
AU  - Springstead JR
AD  - Department of Chemical and Paper Engineering, Western Michigan University, 
      Kalamazoo, MI, USA.
FAU - Mendelson, Michael M
AU  - Mendelson MM
AUID- ORCID: 0000-0001-7590-3958
AD  - Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
FAU - Joehanes, Roby
AU  - Joehanes R
AD  - Population Sciences Branch, Division of Intramural Research, National Heart, 
      Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Levy, Daniel
AU  - Levy D
AD  - Population Sciences Branch, Division of Intramural Research, National Heart, 
      Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Zanoni, Ivan
AU  - Zanoni I
AUID- ORCID: 0000-0002-3423-7474
AD  - Division of Immunology and Division of Gastroenterology, Boston Children's 
      Hospital, Harvard Medical School, Boston, MA, USA. 
      ivan.zanoni@childrens.harvard.edu.
AD  - Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, 
      Italy. ivan.zanoni@childrens.harvard.edu.
LA  - eng
GR  - HHSN268201500001C/HL/NHLBI NIH HHS/United States
GR  - R01 AI121066/AI/NIAID NIH HHS/United States
GR  - P30 DK034854/DK/NIDDK NIH HHS/United States
GR  - HHSN268201500001I/HL/NHLBI NIH HHS/United States
GR  - R01 DK115217/DK/NIDDK NIH HHS/United States
GR  - N01HC25195/HL/NHLBI NIH HHS/United States
GR  - R15 HL121770/HL/NHLBI NIH HHS/United States
GR  - K99 HL136875/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191125
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Alarmins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pathogen-Associated Molecular Pattern Molecules)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine)
SB  - IM
CIN - Nat Rev Immunol. 2020 Jan;20(1):1. PMID: 31792373
MH  - Alarmins/*immunology
MH  - Animals
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Female
MH  - Glycolysis/physiology
MH  - Hypercholesterolemia/immunology/pathology
MH  - Inflammation/prevention & control
MH  - Lipopolysaccharides/*immunology
MH  - Macrophages/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxidation-Reduction
MH  - Oxidative Phosphorylation
MH  - Pathogen-Associated Molecular Pattern Molecules/*immunology
MH  - Phosphatidylcholines/*immunology
MH  - Plaque, Atherosclerotic/pathology/prevention & control
PMC - PMC6923570
MID - NIHMS1541070
EDAT- 2019/11/27 06:00
MHDA- 2020/04/16 06:00
PMCR- 2020/05/25
CRDT- 2019/11/27 06:00
PHST- 2019/02/28 00:00 [received]
PHST- 2019/10/07 00:00 [accepted]
PHST- 2019/11/27 06:00 [pubmed]
PHST- 2020/04/16 06:00 [medline]
PHST- 2019/11/27 06:00 [entrez]
PHST- 2020/05/25 00:00 [pmc-release]
AID - 10.1038/s41590-019-0539-2 [pii]
AID - 10.1038/s41590-019-0539-2 [doi]
PST - ppublish
SO  - Nat Immunol. 2020 Jan;21(1):42-53. doi: 10.1038/s41590-019-0539-2. Epub 2019 Nov 
      25.