Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
1996-7-18
|
| pubmed:abstractText |
Interleukin-6 (IL-6) is the major growth factor for myeloma cells and is believed to participate in the pathogenesis of chronic autoimmune diseases and postmenopausal osteoporosis. IL-6 has been recently shown to possess three topologically distinct receptor binding sites: site 1 for binding to the subunit specific chain IL-6R alpha and sites 2 and 3 for the interaction with two subunits of the signaling chain gp130. We have generated a set of IL-6 variants that behave as potent cytokine receptor super-antagonists carrying substitutions that abolish interaction with gp130 at either site 2 alone (site 2 antagonist) or at both sites 2 and 3 (site 2 + 3 antagonist). In addition, substitutions have been introduced in site 1 that lead to variable increases in binding for IL-6R alpha up to 70-fold. IL-6 super-antagonists inhibit wild-type cytokine activity with efficacy proportional to the increase in receptor binding on a variety of human call lines of different origin, and the most potent molecules display full antagonism at low molar excess to wild-type IL-6. When tested on a representative set of IL-6-dependent human myeloma cell lines, although site 2 super-antagonists were in general quite effective, only the site 2 + 3 antagonist Sant7 showed antagonism on the full spectrum of cells tested. In conclusion, IL-6 super-antagonists are a useful tool for the study of myeloma in vitro and might constitute, in particular Sant7, effective IL-6 blocking agents in vivo.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-phenyl-5,5-dimethyltetrahydro-1,4-...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
87
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4510-9
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8639818-Antigens, CD,
pubmed-meshheading:8639818-Carcinoma, Hepatocellular,
pubmed-meshheading:8639818-Growth Inhibitors,
pubmed-meshheading:8639818-Humans,
pubmed-meshheading:8639818-Interleukin-6,
pubmed-meshheading:8639818-Liver Neoplasms,
pubmed-meshheading:8639818-Melanoma,
pubmed-meshheading:8639818-Models, Molecular,
pubmed-meshheading:8639818-Morpholines,
pubmed-meshheading:8639818-Multiple Myeloma,
pubmed-meshheading:8639818-Neoplasm Proteins,
pubmed-meshheading:8639818-Peptide Fragments,
pubmed-meshheading:8639818-Polymerase Chain Reaction,
pubmed-meshheading:8639818-Protein Conformation,
pubmed-meshheading:8639818-Receptors, Interleukin,
pubmed-meshheading:8639818-Receptors, Interleukin-6,
pubmed-meshheading:8639818-Recombinant Fusion Proteins,
pubmed-meshheading:8639818-Structure-Activity Relationship,
pubmed-meshheading:8639818-Tumor Cells, Cultured
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Human interleukin-6 receptor super-antagonists with high potency and wide spectrum on multiple myeloma cells.
|
| pubmed:affiliation |
Istituto di Richerche di Biologia Molecolare (IRBM)- P. Angeletti, Pomezia, Rome, Italy.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|