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dc.contributor.authorClarke, R.M.
dc.contributor.authorLyons, A.
dc.contributor.authorO'Connell, F.
dc.contributor.authorDeighan, B.F.
dc.contributor.authorBarry, C.E.
dc.contributor.authorAnyakoha, Ngozi G.
dc.contributor.authorNicolaou, Anna
dc.contributor.authorLynch, M.A.
dc.date.accessioned2010-12-16T15:15:03Z
dc.date.available2010-12-16T15:15:03Z
dc.date.issued2008
dc.identifier.citationClarke, R. M., Lyons, A., O'Connell, F., Deighan, B. F., Barry, C. E., Anyakoha, N. G., Nicolaou, A. and Lynch, M. A. (2008). A pivotal role for interleukin-4 in atorvastatin-associated neuroprotection in rat brain. Journal of Biological Chemistry, Vol. 283, No. 4, pp. 1808-1817.en
dc.identifier.urihttp://hdl.handle.net/10454/4587
dc.descriptionnoen
dc.description.abstractInflammatory changes, characterized by an increase in pro-inflammatory cytokine production and up-regulation of the corresponding signaling pathways, have been described in the brains of aged rats and rats treated with the potent immune modulatory molecule lipopolysaccharide (LPS). These changes have been coupled with a deficit in long-term potentiation (LTP) in hippocampus. The evidence suggests that anti-inflammatory agents, which attenuate the LPS-induced and age-associated increase in hippocampal interleukin-1ß (IL-1ß) concentration, lead to restoration of LTP. Here we report that atorvastatin, a member of the family of agents that act as inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, exerts powerful anti-inflammatory effects in brain and that these effects are mediated by IL-4 and independent of its cholesterol-lowering actions. Treatment of rats with atorvastatin increased IL-4 concentration in hippocampal tissue prepared from LPS-treated and aged rats and abrogated the age-related and LPS-induced increases in pro-inflammatory cytokines, interferon-¿ (IFN¿) and IL-1ß, and the accompanying deficit in LTP. The effect of atorvastatin on the LPS-induced increases in IFN¿ and IL-1ß was absent in tissue prepared from IL-4¿/¿ mice. The increase in IL-1ß in LPS-treated and aged rats is associated with increased microglial activation, assessed by analysis of major histocompatibility complex II expression, and the evidence suggests that IFN¿ may trigger this activation. We propose that the primary effect of atorvastatin is to increase IL-4, which antagonizes the effects of IFN¿, the associated increase in microglial activation, and the subsequent cascade of events.en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1074/jbc.M707442200en
dc.subjectAtorvastatinen
dc.subjectBrainen
dc.subjectInflamationen
dc.subjectAnti-inflammatory effectsen
dc.subjectRat modelen
dc.subjectInterleukin-4en
dc.titleA pivotal role for interleuking-4 in Atorvastatin-associated neuroprotection in rat brain.en
dc.status.refereedyesen
dc.typeArticleen
dc.identifier.JournalTitleJournal of Biological Chemistryen
dc.type.versionpublished version paperen
refterms.dateFOA2018-07-19T04:23:17Z


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