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dc.contributor.authorWann, AKen_US
dc.contributor.authorThompson, CLen_US
dc.contributor.authorChapple, JPen_US
dc.contributor.authorKnight, MMen_US
dc.date.accessioned2015-12-07T10:27:32Z
dc.date.available2013-11-19en_US
dc.date.issued2013-12-13en_US
dc.identifier.issn2046-2530en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/9615
dc.description.abstractBACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation.en_US
dc.format.extent17 - ?en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofCiliaen_US
dc.titleInterleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.en_US
dc.typeArticle
dc.rights.holder© Wann et al.; licensee BioMed Central Ltd. 2013
dc.identifier.doi10.1186/2046-2530-2-17en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/24330727en_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
pubs.volume2en_US
dcterms.dateAccepted2013-11-19en_US


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