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Article: 2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation

Title2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation
Authors
KeywordsCalcium signaling
Autoimmunity
Issue Date2012
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 51, p. 21034-21039 How to Cite?
AbstractThe endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-κB and activator protein 1 (AP-1) activation were not adversely affected.Wetherefore propose that2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.
Persistent Identifierhttp://hdl.handle.net/10722/292034
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDuncan, Gordon S.-
dc.contributor.authorBrenner, Dirk-
dc.contributor.authorTusche, Michael W.-
dc.contributor.authorBrus̈tle, Anne-
dc.contributor.authorKnobbe, Christiane B.-
dc.contributor.authorElia, Andrew J.-
dc.contributor.authorMock, Thomas-
dc.contributor.authorBray, Mark R.-
dc.contributor.authorKrammer, Peter H.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:55:38Z-
dc.date.available2020-11-17T14:55:38Z-
dc.date.issued2012-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 51, p. 21034-21039-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292034-
dc.description.abstractThe endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-κB and activator protein 1 (AP-1) activation were not adversely affected.Wetherefore propose that2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectCalcium signaling-
dc.subjectAutoimmunity-
dc.title2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1215558110-
dc.identifier.pmid23213242-
dc.identifier.pmcidPMC3529073-
dc.identifier.scopuseid_2-s2.0-84871370448-
dc.identifier.volume109-
dc.identifier.issue51-
dc.identifier.spage21034-
dc.identifier.epage21039-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000313123700060-
dc.identifier.issnl0027-8424-

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