Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-12-11
pubmed:abstractText
This study addresses a mechanism by which lymphocytes may promote vascular endothelial growth factor (VEGF) expression and angiogenesis in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA (mRNA) by reverse transcription polymerase chain reaction and ribonuclease protection assay with little or no change in expression following activation by cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1, interferon gamma, or IL-4. In contrast, treatment of HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a marked dose-dependent induction of VEGF mRNA (approximately 4-fold), which peaked between 1 and 5 hours post-stimulation. Transient transfection of HUVECs was performed with a luciferase reporter construct under the control of the human VEGF promoter. Treatment of transfected HUVECs with sCD40L was found to enhance luciferase activity (approximately 4-fold) compared with controls, similar to the relative fold induction in mRNA expression in parallel cultures. Thus, CD40-dependent VEGF expression was a result of transcriptional control mechanisms. Treatment of HUVECs with sCD40L was also found to function in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and nude mice induced VEGF expression and marked angiogenesis in vivo. Taken together, these findings are consistent with a function for CD40L-CD40 interactions in VEGF-induced angiogenesis and define a mechanistic link between the immune response and angiogenesis. (Blood. 2000;96:3801-3808)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3801-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11090063-Animals, pubmed-meshheading:11090063-Antigens, CD40, pubmed-meshheading:11090063-CD4-Positive T-Lymphocytes, pubmed-meshheading:11090063-CD40 Ligand, pubmed-meshheading:11090063-Cytokines, pubmed-meshheading:11090063-Electrophoresis, Agar Gel, pubmed-meshheading:11090063-Endothelial Growth Factors, pubmed-meshheading:11090063-Endothelium, Vascular, pubmed-meshheading:11090063-Humans, pubmed-meshheading:11090063-Lymphokines, pubmed-meshheading:11090063-Mice, pubmed-meshheading:11090063-Mice, Nude, pubmed-meshheading:11090063-Mice, SCID, pubmed-meshheading:11090063-Monocytes, pubmed-meshheading:11090063-Neovascularization, Physiologic, pubmed-meshheading:11090063-Promoter Regions, Genetic, pubmed-meshheading:11090063-RNA, Messenger, pubmed-meshheading:11090063-Skin, pubmed-meshheading:11090063-Skin Transplantation, pubmed-meshheading:11090063-Solubility, pubmed-meshheading:11090063-Umbilical Veins, pubmed-meshheading:11090063-Vascular Endothelial Growth Factor A, pubmed-meshheading:11090063-Vascular Endothelial Growth Factors
pubmed:year
2000
pubmed:articleTitle
Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo.
pubmed:affiliation
The Division of Nephrology, Department of Medicine, Children's Hospital, Longwood, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't