The role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotype

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dc.contributor.authorNiklander, Sven E.
dc.contributor.authorCrane, Hannah L.
dc.contributor.authorDarda, Lav
dc.contributor.authorLambert, Daniel W.
dc.contributor.authorHunter, Keith D.
dc.date.accessioned2022-07-27T19:03:39Z
dc.date.available2022-07-27T19:03:39Z
dc.date.issued2021-02
dc.descriptionIndexación Scopuses
dc.description.abstractThere is compelling evidence that senescent cells, through the senescence-associated secretory phenotype (SASP), can promote malignant transformation and invasion. Interleukin-1 (IL-1) is a key mediator of this cytokine network, but the control of its activity in the senescence programme has not been elucidated. IL-1 signalling is regulated by IL-1RA, which has four variants. Here, we show that expression of intracellular IL-1RA type 1 (icIL-1RA1), which competitively inhibits binding of IL-1 to its receptor, is progressively lost during oral carcinogenesis ex vivo and that the pattern of expression is associated with keratinocyte replicative fate in vitro. We demonstrate that icIL-1RA1 is an important regulator of the SASP in mortal cells, as CRISPR/Cas9-mediated icIL-1RA1 knockdown in normal and mortal dysplastic oral keratinocytes is followed by increased IL-6 and IL-8 secretion, and rapid senescence following release from RhoA-activated kinase inhibition. Thus, we suggest that downregulation of icIL-1RA1 in early stages of the carcinogenesis process can enable the development of a premature and deregulated SASP, creating a pro-inflammatory state in which cancer is more likely to arise.en
dc.identifier.citationJournal of Cell Science Volume 134, Issue 4 February 2021 Article number jcs252080es
dc.identifier.doi10.1242/jcs.252080en
dc.identifier.issn0021-9533
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/23356
dc.language.isoenes
dc.publisherCompany of Biologists Ltden
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectHead and neck canceren
dc.subjectIL-1RAen
dc.subjectInterleukin 1 receptor antagonisten
dc.subjectSASPen
dc.subjectSenescenceen
dc.titleThe role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotypeen
dc.typeArtículoen
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