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dc.contributor.authorHerrero, Lara J
dc.contributor.authorNelson, Michelle
dc.contributor.authorSrikiatkhachorn, Anon
dc.contributor.authorGu, Ran
dc.contributor.authorAnantapreecha, Surapee
dc.contributor.authorFingerle-Rowson, Guenter
dc.contributor.authorBucala, Richard
dc.contributor.authorMorand, Eric
dc.contributor.authorSantos, Leilani L
dc.contributor.authorMahalingam, Suresh
dc.date.accessioned2017-05-03T14:38:07Z
dc.date.available2017-05-03T14:38:07Z
dc.date.issued2011
dc.date.modified2012-04-10T23:44:14Z
dc.identifier.issn0027-8424
dc.identifier.doi10.1073/pnas.1101089108
dc.identifier.urihttp://hdl.handle.net/10072/44391
dc.description.abstractArthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis, mayaro and o'nyong-nyong viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphavirus-induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum and tissues, which corresponded to severe inflammation and tissue damage. MIF-deficient (MIF-/-) mice developed mild disease accompanied by a reduction in inflammatory infiltrates and muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF-/- mice exacerbated RRV disease and treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphavirus-induced musculoskeletal disease and may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom12048
dc.relation.ispartofpageto12053
dc.relation.ispartofissue29
dc.relation.ispartofjournalProceedings of the National Academy of Sciences of USA
dc.relation.ispartofvolume108
dc.rights.retentionY
dc.subject.fieldofresearchHumoural immunology and immunochemistry
dc.subject.fieldofresearchcode320405
dc.titleCritical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.date.issued2011
gro.hasfulltextNo Full Text
gro.griffith.authorMahalingam, Suresh
gro.griffith.authorHerrero, Lara J.


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