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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-7-23
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pubmed:abstractText |
Angiogenesis, or new blood vessel growth, is a key process in the development of synovial inflammation in rheumatoid arthritis (RA). Integral to this pathologic proliferation are proinflammatory cytokines. We hypothesized a role for IL-18 as an angiogenic mediator in RA. We examined the effect of human IL-18 on human microvascular endothelial cell (HMVEC) migration. IL-18 induced HMVEC migration at 1 nM (p < 0.05). RA synovial fluids potently induced endothelial cell migration, but IL-18 immunodepletion resulted in a 68 +/- 5% decrease in HMVEC migration (p < 0.05). IL-18 appears to act on HMVECs via alpha(v)beta(3) integrin. To test whether IL-18 induced endothelial cell tube formation in vitro, we quantitated the degree of tube formation on Matrigel matrix. IL-18, 1 or 10 nM, resulted in a 77% or 87% increase in tube formation compared with control (p < 0.05). To determine whether IL-18 may be angiogenic in vivo, we implanted IL-18 in Matrigel plugs in mice, and IL-18 at 1 and 10 nM induced angiogenesis (p < 0.05). The angiogenesis observed appears to be independent of the contribution of local TNF-alpha, as evidenced by adding neutralizing anti-TNF-alpha Ab to the Matrigel plugs. In an alternative in vivo model, sponges embedded with IL-18 or control were implanted into mice. IL-18 (10 nM) induced a 4-fold increase in angiogenesis vs the control (p < 0.05). These findings support a novel function for IL-18 as an angiogenic factor in RA and may elucidate a potential therapeutic target for angiogenesis-directed diseases.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inducing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CXCL5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Chemotactic Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Implants,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/matrigel
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1644-53
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11466388-Angiogenesis Inducing Agents,
pubmed-meshheading:11466388-Animals,
pubmed-meshheading:11466388-Arthritis, Rheumatoid,
pubmed-meshheading:11466388-Cell Division,
pubmed-meshheading:11466388-Cell Line,
pubmed-meshheading:11466388-Cell Migration Inhibition,
pubmed-meshheading:11466388-Cell Movement,
pubmed-meshheading:11466388-Chemokine CXCL5,
pubmed-meshheading:11466388-Chemokines,
pubmed-meshheading:11466388-Chemokines, CXC,
pubmed-meshheading:11466388-Chemotactic Factors,
pubmed-meshheading:11466388-Collagen,
pubmed-meshheading:11466388-Drug Combinations,
pubmed-meshheading:11466388-Drug Implants,
pubmed-meshheading:11466388-Endothelium, Vascular,
pubmed-meshheading:11466388-Granuloma,
pubmed-meshheading:11466388-Humans,
pubmed-meshheading:11466388-Immune Sera,
pubmed-meshheading:11466388-Interleukin-18,
pubmed-meshheading:11466388-Interleukin-8,
pubmed-meshheading:11466388-Laminin,
pubmed-meshheading:11466388-Mice,
pubmed-meshheading:11466388-Mice, Inbred C57BL,
pubmed-meshheading:11466388-Neovascularization, Physiologic,
pubmed-meshheading:11466388-Porifera,
pubmed-meshheading:11466388-Proteoglycans,
pubmed-meshheading:11466388-Receptors, Vitronectin,
pubmed-meshheading:11466388-Recombinant Proteins,
pubmed-meshheading:11466388-Synovial Fluid,
pubmed-meshheading:11466388-Tumor Necrosis Factor-alpha
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pubmed:year |
2001
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pubmed:articleTitle |
Evidence of IL-18 as a novel angiogenic mediator.
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pubmed:affiliation |
Department of Medicine, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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