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

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dc.contributor.authorSven E., Niklander,
dc.contributor.authorHannah L, Crane,
dc.contributor.authorLav, Darda,
dc.contributor.authorLambert, Daniel W.
dc.contributor.authorHunter, Keith D
dc.date.accessioned2022-05-13T00:15:34Z
dc.date.available2022-05-13T00:15:34Z
dc.date.issued2021-02
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. © 2021 Company of Biologists Ltd. All rights reserved.es
dc.description.sponsorshipIndexación: Scopuses
dc.identifier.citationJournal of Cell ScienceOpen AccessVolume 134, Issue 4February 2021 Article number jcs252080es
dc.identifier.issn00219533
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/22512
dc.language.isoenes
dc.publisherCompany of Biologists Ltdes
dc.subjectHead and neck cancer; IL-1RA; Interleukin 1 receptor antagonist; SASP; Senescencees
dc.titleThe role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotypees
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