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dc.contributor.author | Acosta, Y Y | |
dc.contributor.author | Montes-Casado, Maria | |
dc.contributor.author | Aragoneses-Fenoll, Laura | |
dc.contributor.author | Dianzani, U | |
dc.contributor.author | Portoles, Pilar | |
dc.contributor.author | Rojo, J M | |
dc.date.accessioned | 2020-06-01T07:57:00Z | |
dc.date.available | 2020-06-01T07:57:00Z | |
dc.date.issued | 2014-01 | |
dc.identifier.citation | Int J Immunopathol Pharmacol. 2014 Jan-Mar;27(1):53-67. | es_ES |
dc.identifier.issn | 0394-6320 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10237 | |
dc.description | Corrigendum: Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75. Int J Immunopathol Pharmacol. 2015 Mar;28(1):146. doi: 10.1177/0394632015572738. PMID: 25816420. | |
dc.description.abstract | Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110alpha catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-gamma production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (less than 10 nM) inhibited IFN-gamma, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival. | es_ES |
dc.description.sponsorship | Y.Y.A. is recipient of a Predoctoral Fellowship of the "Junta deAmpliacion de Estudios" (JAE) Program (e.S.I.e., Ministerio de Ciencia e Innovacion, Spain). P.P. is a Tenured Sciencist of e.S.I.e. at the Centro Nacional de Microbiologia, Instituto de Salud Carlos III. This work was supported by Grants PI070620, PI070484 (Plan Estatal I+D+i, ISCIIISubdireccion General de Evaluaci6n y Fomento de la Investigacion, Ministerio de Economia y Competitividad, Spain) to J.M.R. and P.P, and by Associazione Italiana Ricerca sui Cancro (AIRC, Milan) to U.D. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | SAGE Publishing | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Apoptosis | es_ES |
dc.subject.mesh | CD4-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Cytokines | es_ES |
dc.subject.mesh | Dose-Response Relationship, Drug | es_ES |
dc.subject.mesh | Encephalomyelitis, Autoimmune, Experimental | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Hydrazones | es_ES |
dc.subject.mesh | Lymphocyte Activation | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Sulfonamides | es_ES |
dc.subject.mesh | Phosphoinositide-3 Kinase Inhibitors | es_ES |
dc.title | Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75 | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 24674679 | es_ES |
dc.format.volume | 27 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 53-67 | es_ES |
dc.identifier.doi | 10.1177/039463201402700108 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1177/039463201402700108 | es_ES |
dc.identifier.journal | International journal of immunopathology and pharmacology | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/PI070620, | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/PI070484 | es_ES |
dc.rights.accessRights | open access | es_ES |