PMID- 20354139
OWN - NLM
STAT- MEDLINE
DCOM- 20100907
LR  - 20211020
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 24
IP  - 8
DP  - 2010 Aug
TI  - Interleukin-10 overexpression in macrophages suppresses atherosclerosis in 
      hyperlipidemic mice.
PG  - 2869-80
LID - 10.1096/fj.09-148155 [doi]
AB  - In atherogenesis, macrophage foam cell formation is modulated by pathways 
      involving both the uptake and efflux of cholesterol. We recently showed that 
      interleukin-10 (IL-10) modulates lipid metabolism by enhancing both uptake and 
      efflux of cholesterol in macrophages. However, the mechanistic details of these 
      properties in vivo have been unclear. Thus, the purpose of this study was to 
      determine whether expression of IL-10 in macrophages would alter susceptibility 
      to atherosclerosis and whether IL-10 exerts its antiatherosclerotic properties by 
      modulating lipid metabolism in macrophages. We utilized a macrophage-specific 
      retroviral vector that allows long-term in vivo expression of IL-10 in 
      macrophages through transplantation of retrovirally transduced bone marrow cells 
      (BMCs). IL-10 expressed by macrophages derived from transduced BMCs inhibited 
      atherosclerosis in LDLR(-/-) mice by reducing cholesteryl ester accumulation in 
      atherosclerotic sites. Experiments with primary macrophages indicated that 
      macrophage source of IL-10 stimulated both the uptake (by up-regulating scavenger 
      receptors) and efflux of cholesterol (by activating the PPARgamma-LXR-ABCA1/ABCG1 
      pathway), thereby reducing inflammation and apoptosis in atherosclerosis. These 
      findings indicate that BMC-transduced macrophage IL-10 production can act as a 
      strong antiatherogenic agent, and they highlight a novel antiatherosclerotic 
      therapy using a simple, yet effective, stem cell transduction system that 
      facilitates long-term expression of IL-10 in macrophages.
FAU - Han, Xinbing
AU  - Han X
AD  - Vascular Medicine Research Unit, Brigham Women's Hospital, Harvard Medical 
      School, Cambridge, Massachusetts, USA.
FAU - Kitamoto, Shiro
AU  - Kitamoto S
FAU - Wang, Hongwei
AU  - Wang H
FAU - Boisvert, William A
AU  - Boisvert WA
LA  - eng
GR  - R01 HL075677/HL/NHLBI NIH HHS/United States
GR  - HL075677/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100330
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Atherosclerosis/*drug therapy/pathology
MH  - Genetic Therapy
MH  - Hyperlipidemias/*complications
MH  - Inflammation
MH  - Interleukin-10/biosynthesis/*genetics/pharmacology
MH  - Lipid Metabolism/drug effects
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Transduction, Genetic
PMC - PMC2909283
EDAT- 2010/04/01 06:00
MHDA- 2010/09/08 06:00
PMCR- 2011/08/01
CRDT- 2010/04/01 06:00
PHST- 2010/04/01 06:00 [entrez]
PHST- 2010/04/01 06:00 [pubmed]
PHST- 2010/09/08 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - fj.09-148155 [pii]
AID - 09-148155 [pii]
AID - 10.1096/fj.09-148155 [doi]
PST - ppublish
SO  - FASEB J. 2010 Aug;24(8):2869-80. doi: 10.1096/fj.09-148155. Epub 2010 Mar 30.