PMID- 30282830
OWN - NLM
STAT- MEDLINE
DCOM- 20191213
LR  - 20191217
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 3
IP  - 19
DP  - 2018 Oct 4
TI  - Myeloid HO-1 modulates macrophage polarization and protects against 
      ischemia-reperfusion injury.
LID - 120596 [pii]
LID - 10.1172/jci.insight.120596 [doi]
LID - e120596
AB  - Macrophages polarize into heterogeneous proinflammatory M1 and antiinflammatory 
      M2 subtypes. Heme oxygenase 1 (HO-1) protects against inflammatory processes such 
      as ischemia-reperfusion injury (IRI), organ transplantation, and atherosclerosis. 
      To test our hypothesis that HO-1 regulates macrophage polarization and protects 
      against IRI, we generated myeloid-specific HO-1-knockout (mHO-1-KO) and 
      -transgenic (mHO-1-Tg) mice, with deletion or overexpression of HO-1, in various 
      macrophage populations. Bone marrow-derived macrophages (BMDMs) from mHO-1-KO 
      mice, treated with M1-inducing LPS or M2-inducing IL-4, exhibited increased mRNA 
      expression of M1 (CXCL10, IL-1beta, MCP1) and decreased expression of M2 (Arg1 and 
      CD163) markers as compared with controls, while BMDMs from mHO-1-Tg mice 
      displayed the opposite. A similar pattern was observed in the hepatic M1/M2 
      expression profile in a mouse model of liver IRI. mHO-1-KO mice displayed 
      increased hepatocellular damage, serum AST/ALT levels, Suzuki's histological 
      score of liver IRI, and neutrophil and macrophage infiltration, while mHO-1-Tg 
      mice exhibited the opposite. In human liver transplant biopsies, subjects with 
      higher HO-1 levels showed lower expression of M1 markers together with decreased 
      hepatocellular damage and improved outcomes. In conclusion, myeloid HO-1 
      expression modulates macrophage polarization, and protects against liver IRI, at 
      least in part by favoring an M2 phenotype.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Medicine, Division of Cardiology, and.
FAU - Nakamura, Kojiro
AU  - Nakamura K
AD  - Department of Surgery, David Geffen School of Medicine, University of California, 
      Los Angeles, California, USA.
FAU - Kageyama, Shoichi
AU  - Kageyama S
AD  - Department of Surgery, David Geffen School of Medicine, University of California, 
      Los Angeles, California, USA.
FAU - Lawal, Akeem O
AU  - Lawal AO
AD  - Department of Medicine, Division of Cardiology, and.
FAU - Gong, Ke Wei
AU  - Gong KW
AD  - Department of Medicine, Division of Cardiology, and.
FAU - Bhetraratana, May
AU  - Bhetraratana M
AD  - Department of Medicine, Division of Cardiology, and.
FAU - Fujii, Takehiro
AU  - Fujii T
AD  - Department of Surgery, David Geffen School of Medicine, University of California, 
      Los Angeles, California, USA.
FAU - Sulaiman, Dawoud
AU  - Sulaiman D
AD  - Department of Medicine, Division of Cardiology, and.
FAU - Hirao, Hirofumi
AU  - Hirao H
AD  - Department of Surgery, David Geffen School of Medicine, University of California, 
      Los Angeles, California, USA.
FAU - Bolisetty, Subhashini
AU  - Bolisetty S
AD  - Department of Medicine, University of Alabama, Tuscaloosa, Alabama, USA.
FAU - Kupiec-Weglinski, Jerzy W
AU  - Kupiec-Weglinski JW
AD  - Department of Surgery, David Geffen School of Medicine, University of California, 
      Los Angeles, California, USA.
FAU - Araujo, Jesus A
AU  - Araujo JA
AD  - Department of Medicine, Division of Cardiology, and.
AD  - Department of Environmental Health Sciences, Fielding School of Public Health, 
      University of California, Los Angeles, California, USA.
LA  - eng
GR  - R01 ES016959/ES/NIEHS NIH HHS/United States
GR  - R56 ES016959/ES/NIEHS NIH HHS/United States
GR  - T32 ES015457/ES/NIEHS NIH HHS/United States
GR  - K01 DK103931/DK/NIDDK NIH HHS/United States
GR  - R01 DK062357/DK/NIDDK NIH HHS/United States
GR  - R01 DK107533/DK/NIDDK NIH HHS/United States
GR  - R01 DK102110/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181004
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Membrane Proteins)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allografts/blood supply/cytology/pathology
MH  - Animals
MH  - Biopsy
MH  - Disease Models, Animal
MH  - Female
MH  - Graft Rejection/diagnosis/*immunology/pathology
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Humans
MH  - Liver/blood supply/cytology/pathology
MH  - Liver Function Tests
MH  - Liver Transplantation/*adverse effects
MH  - Macrophages/*immunology/metabolism
MH  - Male
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Reperfusion Injury/diagnosis/*immunology/pathology
MH  - Signal Transduction/immunology
MH  - Young Adult
PMC - PMC6237471
OTO - NOTNLM
OT  - Hepatology
OT  - Inflammation
OT  - Innate immunity
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2018/10/05 06:00
MHDA- 2019/12/18 06:00
PMCR- 2018/10/04
CRDT- 2018/10/05 06:00
PHST- 2018/02/21 00:00 [received]
PHST- 2018/08/21 00:00 [accepted]
PHST- 2018/10/05 06:00 [entrez]
PHST- 2018/10/05 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/10/04 00:00 [pmc-release]
AID - 120596 [pii]
AID - 10.1172/jci.insight.120596 [doi]
PST - epublish
SO  - JCI Insight. 2018 Oct 4;3(19):e120596. doi: 10.1172/jci.insight.120596.