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rdf:type |
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lifeskim:mentions |
umls-concept:C0001128,
umls-concept:C0034857,
umls-concept:C0205314,
umls-concept:C0205460,
umls-concept:C0441655,
umls-concept:C0521119,
umls-concept:C0679058,
umls-concept:C0679622,
umls-concept:C1337092,
umls-concept:C1413188,
umls-concept:C1514562,
umls-concept:C1547699,
umls-concept:C1709915,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2700640
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pubmed:issue |
1
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pubmed:dateCreated |
2009-6-22
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pubmed:abstractText |
CCL2 is a key CC chemokine that has been implicated in a variety of inflammatory autoimmune diseases and in tumor progression and it is therefore an important target for therapeutic intervention in these diseases. Soluble receptor-based therapy is a known approach for neutralizing the in vivo functions of soluble mediators. Owing to the complexity of seven-transmembrane G protein-coupled receptors, efforts to generate neutralizing soluble chemokine receptors have so far failed. We developed a strategy that is based on the generation of short recombinant proteins encoding different segments of a G protein-coupled receptor, and tested the ability of each of them to bind and neutralize its target chemokine. We show that a fusion protein comprised of as few as 20 aa of the third extracellular (E3) domain of the CCL2 receptor, stabilized by the IgG H chain Fc domain (E3-IgG or BL-2030), selectively binds CCL2 and CCL16 and effectively neutralizes their biological activities. More importantly, E3-IgG (BL-2030) could effectively suppress the in vivo biological activity of CCL2, attenuating ongoing experimental autoimmune encephalomyelitis, as well as the development of human prostate tumor in SCID mice.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
732-9
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pubmed:meshHeading |
pubmed-meshheading:19535619-Animals,
pubmed-meshheading:19535619-Cell Line,
pubmed-meshheading:19535619-Cell Line, Tumor,
pubmed-meshheading:19535619-Cell Migration Inhibition,
pubmed-meshheading:19535619-Cell Proliferation,
pubmed-meshheading:19535619-Chemokine CCL2,
pubmed-meshheading:19535619-Female,
pubmed-meshheading:19535619-Humans,
pubmed-meshheading:19535619-Male,
pubmed-meshheading:19535619-Mice,
pubmed-meshheading:19535619-Mice, Inbred BALB C,
pubmed-meshheading:19535619-Mice, Inbred C57BL,
pubmed-meshheading:19535619-Mice, SCID,
pubmed-meshheading:19535619-Prostatic Neoplasms,
pubmed-meshheading:19535619-Protein Binding,
pubmed-meshheading:19535619-Protein Structure, Tertiary,
pubmed-meshheading:19535619-Receptors, CCR2,
pubmed-meshheading:19535619-Recombinant Fusion Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
A novel recombinant fusion protein encoding a 20-amino acid residue of the third extracellular (E3) domain of CCR2 neutralizes the biological activity of CCL2.
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pubmed:affiliation |
Department of Immunology, Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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