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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1990-10-12
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pubmed:abstractText |
In order to segregate multiple activities ascribed to IL-1, various human IL-1 alpha derivatives were produced by recombinant DNA technology. A derivative substituted at the 151st Asp with Tyr(termed to be TN-55) showed unique characteristics. TN-55 lost the PGE2 inducing activity in a human osteosarcoma cell line (MG-63) and growth promoting activity for a human dermal fibroblast cell line (CCD-27Sk), but partially remained LAF activity in mouse thymocyte, cytostatic activity against a human melanoma cell line (A-375) and IL-2 inducing activity in a human T cell line (HSB.2). Although TN-55 bound to the receptor on MG-63 cells with a similar affinity as native IL-1 alpha, TN-55 not only failed in inducing PGE2 production but also antagonized the PGE2 inducing action of IL-1 alpha or IL-1 beta. Thus, TN-55 seems to work as a receptor antagonist. Moreover, TN-55 did not stimulate ACTH secretion in rats in vivo. On the other hand, TN-55 induced PGE2 production in a rabbit dermal fibroblast cell line (RAB-9) and exhibited pyrogenicity in rabbits in vivo. These data suggest that TN-55 has different species-cross reactivity from native IL-1 alpha. In conclusion, multiple biological activities of IL-1 alpha can be segregated by substituting one amino acid. TN-55 may be an ideal IL-1 agonist which lacks inflammatory characteristics of IL-1 (e.g. PGE2-dependent activities) in human but partially retained T lymphocyte stimulating activity and tumor cytostatic activity. In addition, TN-55 may also work as an IL-1 antagonist to block PGE2 production induced by IL-1 through receptor competition.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenocorticotropic Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1
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pubmed:status |
MEDLINE
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pubmed:issn |
0277-6766
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
405-13
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2169012-Adrenocorticotropic Hormone,
pubmed-meshheading:2169012-Amino Acid Sequence,
pubmed-meshheading:2169012-Animals,
pubmed-meshheading:2169012-Binding, Competitive,
pubmed-meshheading:2169012-Cell Line,
pubmed-meshheading:2169012-Cytotoxicity, Immunologic,
pubmed-meshheading:2169012-Dinoprostone,
pubmed-meshheading:2169012-Fever,
pubmed-meshheading:2169012-Humans,
pubmed-meshheading:2169012-Interleukin-1,
pubmed-meshheading:2169012-Lymphocyte Activation,
pubmed-meshheading:2169012-Male,
pubmed-meshheading:2169012-Rats,
pubmed-meshheading:2169012-Rats, Inbred Strains,
pubmed-meshheading:2169012-Receptors, Immunologic,
pubmed-meshheading:2169012-Receptors, Interleukin-1
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pubmed:year |
1990
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pubmed:articleTitle |
A human IL-1 alpha derivative which lacks prostaglandin E2 inducing activity and inhibits the activity of IL-1 through receptor competition.
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pubmed:affiliation |
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
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pubmed:publicationType |
Journal Article
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