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dc.creatorMarballi, Ketan
dc.creatorQuiñones, Marlon
dc.creatorJiménez, Fabio
dc.creatorEscamilla, Michael
dc.creatorRaventós Vorst, Henriette
dc.creatorSoto Bernardini, María Clara
dc.creatorAhuja, Seema S.
dc.creatorWalss Bass, Consuelo
dc.date.accessioned2014-05-15T16:17:53Z
dc.date.available2014-05-15T16:17:53Z
dc.date.issued2010-11
dc.identifier.citationhttp://link.springer.com/article/10.1007/s00109-010-0653-y
dc.identifier.issn0946-2716
dc.identifier.otheressn: 1432-1440
dc.identifier.urihttps://hdl.handle.net/10669/11056
dc.descriptionartículo (arbitrado) -- Universidad de Costa Rica. Centro de Investigaciones en Biología Celular y Molecular, 2010es
dc.description.abstractNeuregulin 1 (NRG1) has been implicated in several disorders including breast cancer, multiple sclerosis, and schizophrenia. Also, recent evidence suggests that NRG1 may play a role in regulation of inflammation and immune system response. We therefore hypothesized that a schizophrenia-associated missense mutation (valine to leucine) we identified within the transmembrane region of NRG1 would also be linked to immune dysregulation. We used plasma samples from families carrying the mutation to measure levels of antibodies to 41 autoimmune markers and six cytokines (IL-1b, IL-6, IL-10, IL-8, IL-12p70, and TNF-α) and used these levels Epstein–Barr virus-transformed B cells from heterozygous mutation carriers and wild-type individuals to evaluate protein and mRNA cytokine expression in vitro using quantitative PCR and ELISA assays. In vivo, increased levels of 25 autoimmune markers as well as elevated levels of cytokines were significantly associated with the NRG1 mutation. In vitro, we observed a significant increase in protein secretion levels of IL-6, TNF-α, and IL-8 in mutation carriers compared with controls. At the mRNA level, we observed a significant increase in IL-6 expression, while IL-4 levels appeared to be downregulated in heterozygous individuals compared with wild-type controls. This is the first report of association of a NRG1 mutation with immune dysregulation. This study could contribute towards understanding the role of NRG1 in the pathogenesis of schizophrenia and other disorders in which inflammation plays an important role.es
dc.description.sponsorshipSupported by grants from the National Institutes of Health (K01MH077777), the Stanley Medical Research Institute, and NARSAD, the mental health research association to CWB.es
dc.language.isoen_USes
dc.publisherJ Mol Med (Berl). 2010 November ; 88(11): 1133–1141es
dc.subjectInmunologiaes
dc.subjectImmune systemes
dc.subjectAutoantibodyes
dc.subjectLymphoblastoid cell lineses
dc.subjectCytokinees
dc.titleIn vivo and in vitro genetic evidence of involvement of neuregulin 1 in immune system dysregulationes
dc.typeartículo original
dc.identifier.doi10.1007/s00109-010-0653-y
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)es


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