| pubmed-article:12417753 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0005974 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C1325331 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0231491 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0533294 | lld:lifeskim |
| pubmed-article:12417753 | lifeskim:mentions | umls-concept:C0301625 | lld:lifeskim |
| pubmed-article:12417753 | pubmed:dateCreated | 2002-11-13 | lld:pubmed |
| pubmed-article:12417753 | pubmed:abstractText | IL-6 is a multifunctional cytokine involved in regulation of differentiation, antibody production, and growth of certain types of tumor cells. Its excessive production plays a major role in pathogenesis of multiple myeloma and postmenopausal osteoporosis. In the course of a screening program aimed at IL-6 inhibitor from microbial products, we found madindoline A (MDL-A) and madindoline B, which have a fuloindoline structure with diketocyclopentene bound to the methyl group. MDL-A has no cytotoxic activities. It inhibited only activities of both IL-6 and IL-11 without affecting the IL-6-specific signal transduction cascade, JAK2/STAT3. In a dose-dependent manner [(3)H]MDL-A binds to gp130, which is a signal transducing 130-kDa glycoprotein, but formation of the trimeric complex IL-6/IL-6 receptor/gp130 was not inhibited, suggesting that MDL-A suppresses dimerization of trimeric complexes. Not only did MDL-A markedly inhibit IL-6- and IL-11-induced osteoclastogenesis in vitro, but it also inhibited IL-6-stimulated serum amyloid A production and bone resorption in an experimental model of postmenopausal osteoporosis in vivo by a different mechanism from that of 17beta-estradiol. Here we show that MDL-A has a highly selective inhibitory effect on IL-6 and IL-11 activities by inhibiting a gp130 activity while suppressing bone loss in ovariectomized mice. MDL-A is anticipated as a lead compound for treatment of hormone-dependent postmenopausal osteoporosis, which has no serious side effects, and as a new mechanism of action, gp130 blocking. | lld:pubmed |
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| pubmed-article:12417753 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12417753 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12417753 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:SunazukaToshi... | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:OmuraSatoshiS | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:HiroseTomoyas... | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:KikuchiYujiY | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:FukamiAkikoA | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:HayashiMasahi... | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:KomiyamaKanki... | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:RhoMun-ChualM... | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:EnomotoAkikoA | lld:pubmed |
| pubmed-article:12417753 | pubmed:author | pubmed-author:KimYong-PilYP | lld:pubmed |
| pubmed-article:12417753 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12417753 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12417753 | pubmed:pagination | 14728-33 | lld:pubmed |
| pubmed-article:12417753 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
| pubmed-article:12417753 | pubmed:articleTitle | Suppression of bone resorption by madindoline A, a novel nonpeptide antagonist to gp130. | lld:pubmed |
| pubmed-article:12417753 | pubmed:affiliation | Kitasato Institute for Life Sciences and School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. | lld:pubmed |
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