PMID- 34071440
OWN - NLM
STAT- MEDLINE
DCOM- 20210922
LR  - 20210922
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 6
DP  - 2021 May 28
TI  - Disulfide and Fully Reduced HMGB1 Induce Different Macrophage Polarization and 
      Migration Patterns.
LID - 10.3390/biom11060800 [doi]
LID - 800
AB  - Macrophage plasticity enables cells to obtain different functions over a broad 
      proinflammatory and repairing spectrum. In different conditions, macrophages can 
      be induced by high-mobility group box 1 (HMGB1), a nuclear DNA-binding protein 
      that activates innate immunity, to polarize towards a pro- (M1) or 
      anti-inflammatory (M2) phenotype. In this study, we investigated the phenotypes 
      of murine bone-marrow-derived macrophages (BMDMs) induced by different HMGB1 
      redox isoforms in depth. Our results demonstrate that disulfide HMGB1 (dsHMGB1) 
      induces a unique macrophage phenotype that secretes pro-inflammatory cytokines, 
      rather than inducing metabolic changes leading to nitric oxide production. Fully 
      reduced HMGB1 (frHMGB1) did not induce macrophage polarization. The migrating 
      function of BMDMs was measured by scratch assay after the stimulation with 
      dsHMGB1 and frHMGB1. Both dsHMGB1 and frHMGB1 induced cell migration. We found 
      that dsHMGB1 mediates cytokine secretion and cellular motility, mainly through 
      toll-like receptor 4 (TLR4). Importantly, our data shows that dsHMGB1 and frHMGB1 
      induce distinct BMDM polarization phenotypes, and that dsHMGB1 induces a unique 
      phenotype differing from the classical proinflammatory macrophage phenotype.
FAU - Salo, Henna
AU  - Salo H
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
FAU - Qu, Heshuang
AU  - Qu H
AUID- ORCID: 0000-0001-6011-5588
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
FAU - Mitsiou, Dimitra
AU  - Mitsiou D
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
FAU - Aucott, Hannah
AU  - Aucott H
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
FAU - Han, Jinming
AU  - Han J
AUID- ORCID: 0000-0002-6084-3275
AD  - Department of Clinical Neuroscience, Centre for Molecular Medicine, Karolinska 
      Institutet, 17176 Stockholm, Sweden.
FAU - Zhang, Xing-Mei
AU  - Zhang XM
AD  - Department of Clinical Neuroscience, Centre for Molecular Medicine, Karolinska 
      Institutet, 17176 Stockholm, Sweden.
FAU - Aulin, Cecilia
AU  - Aulin C
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
FAU - Erlandsson Harris, Helena
AU  - Erlandsson Harris H
AD  - Department of Medicine, Solna, Rheumatology Unit, Centre for Molecular Medicine, 
      Karolinska Institutet, 17176 Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210528
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Disulfides)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Cell Movement/*drug effects
MH  - Disulfides/*chemistry
MH  - Female
MH  - *HMGB1 Protein/chemistry/pharmacology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Oxidation-Reduction
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC8229957
OTO - NOTNLM
OT  - HMGB1
OT  - RAGE
OT  - TLR4
OT  - dsHMGB1
OT  - frHMGB1
OT  - inflammation
OT  - macrophages
OT  - migration
OT  - polarization
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/09/23 06:00
PMCR- 2021/05/28
CRDT- 2021/06/02 01:32
PHST- 2021/05/07 00:00 [received]
PHST- 2021/05/25 00:00 [revised]
PHST- 2021/05/25 00:00 [accepted]
PHST- 2021/06/02 01:32 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/09/23 06:00 [medline]
PHST- 2021/05/28 00:00 [pmc-release]
AID - biom11060800 [pii]
AID - biomolecules-11-00800 [pii]
AID - 10.3390/biom11060800 [doi]
PST - epublish
SO  - Biomolecules. 2021 May 28;11(6):800. doi: 10.3390/biom11060800.