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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-11-5
pubmed:abstractText
Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor, partially through the induction of endothelial cell apoptosis. Here we report that PEDF can also induce the apoptosis of human THP-1 monocytic leukemia cell line-derived macrophage cells (THP-1 macrophages) and peroxisome proliferator-activated receptor gamma (PPARgamma), a pleiotropic transcriptional factor is involved in the signaling. TUNEL and propidium iodide permeability assays demonstrated that PEDF dose- and time-dependently induces both apoptosis and necrosis of THP-1 macrophages while inducing the cleavages of procaspase-9, -3, the release of cytochrome c and the overexpression of p53. All these PEDF effects can be attenuated by either PPARgamma inhibitor GW9662 or PPARgamma small interfering RNA. The effects of PEDF can be reproduced by transient expression of PPARgamma by a PPARgamma-expression plasmid transfection. PEDF increased the expression and transcriptional activity of PPARgamma in THP-1 macrophages. In addition, PEDF also induced apoptosis in primary human monocyte-derived macrophages (MDMs) while inducing the expression of PPARgamma. Our observations indicate that PEDF induces macrophage apoptosis and necrosis through the signaling of PPARgamma. This suggests a novel mechanism through which PEDF can modulate inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
898-909
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Pigment epithelium-derived factor induces THP-1 macrophage apoptosis and necrosis by the induction of the peroxisome proliferator-activated receptor gamma.
pubmed:affiliation
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't