PMID- 20692534
OWN - NLM
STAT- MEDLINE
DCOM- 20110311
LR  - 20211028
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 215
IP  - 9-10
DP  - 2010 Sep-Oct
TI  - IL-10 regulation of macrophage VEGF production is dependent on macrophage 
      polarisation and hypoxia.
PG  - 796-803
LID - 10.1016/j.imbio.2010.05.025 [doi]
AB  - Vascular endothelial growth factor A (VEGF) is critical for vascular remodelling 
      during tissue repair subsequent to inflammation or injury, but under pathological 
      conditions, VEGF induces tissue damaging angiogenesis. Macrophages generate VEGF 
      that supports angiogenesis, when they adapt to their environment and respond with 
      a co-ordinated set of signals to promote or resolve inflammation. Depending on 
      the stimulus, the phenotype of macrophage activation is broadly classified into 
      M1 (NOS2(+)) and M2 (arginase-1(+)). In recent studies, IL-10, an 
      anti-inflammatory cytokine that suppresses the M1 phenotype, has been shown to 
      dampen the angiogenic switch and subsequent neovascularisation. However, as we 
      show here, these effects are context dependent. In this study, we have 
      demonstrated that IL-10 inhibits M1 bone marrow-derived macrophages (BMDMs) VEGF, 
      stimulated by LPS/CGS21680 (adenosine A2A receptor agonist), but does not prevent 
      VEGF production from M2 macrophages stimulated with prostaglandin E2 (PGE2). 
      Furthermore, we show that hypoxic-conditioned BMDM generated VEGF was maintained 
      in the presence of IL-10, but was suppressed when concomitantly stimulated with 
      IFN-gamma. Finally, LPS/PGE2 generated an arginase-1(+) M2 macrophage that in 
      addition to generating VEGF produced significant quantities of IL-10. Under these 
      conditions, neither in IL-10 deficient macrophages nor following IL-10 
      neutralization was VEGF production affected. Our results indicate IL-10 
      suppressed M1 but not M2 derived VEGF, and that activation signals determined the 
      influence of IL-10 on VEGF production. Consequently, therapies to suppress 
      macrophage activation that as a result generate IL-10, or utilising IL-10 as a 
      potential anti-angiogenic therapy, may result in a paradoxical support of 
      neovascularisation and thus on-going tissue damage or aberrant repair.
CI  - Copyright 2010 Elsevier GmbH. All rights reserved.
FAU - Wu, Wei-Kang
AU  - Wu WK
AD  - Department of Clinical Sciences South Bristol, University of Bristol, University 
      Walk, Bristol, UK.
FAU - Llewellyn, Oliver P C
AU  - Llewellyn OP
FAU - Bates, David O
AU  - Bates DO
FAU - Nicholson, Lindsay B
AU  - Nicholson LB
FAU - Dick, Andrew D
AU  - Dick AD
LA  - eng
GR  - R138/1109/DMT_/The Dunhill Medical Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100604
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.5.3.1 (Arginase)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Arginase/biosynthesis
MH  - Cell Differentiation/genetics/immunology
MH  - Cells, Cultured
MH  - Dinoprostone/immunology/metabolism
MH  - Hypoxia/*immunology
MH  - Inflammation
MH  - Interferon-gamma/metabolism
MH  - Interleukin-10/*immunology/metabolism
MH  - Lipopolysaccharides/immunology/metabolism
MH  - Macrophages/immunology/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neovascularization, Pathologic/genetics/*immunology
MH  - RNA, Small Interfering/genetics
MH  - Toll-Like Receptor 4/genetics
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics/metabolism
EDAT- 2010/08/10 06:00
MHDA- 2011/03/12 06:00
CRDT- 2010/08/10 06:00
PHST- 2010/04/08 00:00 [received]
PHST- 2010/05/20 00:00 [accepted]
PHST- 2010/08/10 06:00 [entrez]
PHST- 2010/08/10 06:00 [pubmed]
PHST- 2011/03/12 06:00 [medline]
AID - S0171-2985(10)00091-4 [pii]
AID - 10.1016/j.imbio.2010.05.025 [doi]
PST - ppublish
SO  - Immunobiology. 2010 Sep-Oct;215(9-10):796-803. doi: 10.1016/j.imbio.2010.05.025. 
      Epub 2010 Jun 4.