Show simple item record

dc.contributor.authorLYNCH, MARINAen
dc.contributor.authorMINOGUE, AEDINen
dc.date.accessioned2015-12-09T12:00:02Z
dc.date.available2015-12-09T12:00:02Z
dc.date.issued2015en
dc.date.submitted2015en
dc.identifier.citationRaasay S. Jones, Aed?n M. Minogue, Orla Fitzpatrick, Marina A. Lynch, Inhibition of JAK2 attenuates the increase in inflammatory markers in microglia from APP/PS1 mice, Experimental Cell Research, 36, 10, 2015, 2716?2724en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/75199
dc.descriptionIN_PRESSen
dc.description.abstractThere is a wealth of evidence indicating that macrophages adopt distinct phenotypes when exposed to specific stimuli and, in the past few years, accumulating data suggest that microglia behave somewhat similarly. Therefore, microglia can adopt the so-called M1 or M2 phenotypes in response to interferon-γ (IFNγ) and interleukin-4, respectively. Although it has yet to be unequivocally proven in the context of microglia, acutely activated M1 cells are probably protective, although a persistent M1 state is likely to be damaging, whereas M2 cells may be reparative and restorative. In this case, particularly because the current evidence suggests the development of a predominantly M1 state with age and in neurodegenerative diseases, it is important to identify mechanisms by which polarization of microglia can be modulated. The present findings indicate that exposure of cultured microglia to IFNγ increased expressions of the archetypal markers of the M1 phenotype, tumour necrosis factor-α, and inducible nitric oxide synthase, and preexposure of cells to amyloid-β (Aβ) sensitized microglia to subsequent stimulation with IFNγ. Importantly, this synergy was also evident in microglia prepared from the brains of transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1, APP/PS1 mice) and are exposed to a combination of increasing concentrations of endogenous Aβ from 4 or 5 months of age and an age-related increase in IFNγ. Significantly, the JAK2 inhibitor, TG101209, attenuated the IFNγ-induced changes in cultured microglia and in isolated microglia prepared from APP/PS1 mice. These findings suggest that targeting JAK2 may be a potential strategy for reducing neuroinflammation in Alzheimer's disease.en
dc.description.sponsorshipThis work was funded by Science Foundation Ireland to MAL (11/PI/1014). RSJ, AMM, and OF contributed equally to this work.en
dc.format.extent2716?2724en
dc.relation.ispartofseriesExperimental Cell Researchen
dc.relation.ispartofseries36en
dc.relation.ispartofseries10en
dc.rightsYen
dc.subjectJAK2; M1/M2; TG101209; Microglia; APP/PS1en
dc.subject.lcshJAK2; M1/M2; TG101209; Microglia; APP/PS1en
dc.titleInhibition of JAK2 attenuates the increase in inflammatory markers in microglia from APP/PS1 miceen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lynchmaen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/aminoguen
dc.identifier.rssinternalid105050en
dc.identifier.doihttp://dx.doi.org/10.1016/j.neurobiolaging.2015.04.018en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber11/PI/1014en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record