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

ABSTRACT There is compelling evidence that senescent cells, through the senescence-associated secretory phenotype (SASP), can promote malignant transformation and invasion. Interleukin-1 (IL-1) a key mediator of this cytokine network, but control its activity in senescence programme has not been elucidated. IL-1 signalling regulated by IL-1RA, which four variants. Here, we show expression intracellular IL-1RA type 1 (icIL-1RA1), competitively inhibits binding to receptor, progressively lost during oral carcinogenesis ex vivo pattern associated with keratinocyte replicative fate vitro. We demonstrate icIL-1RA1 an important regulator SASP mortal as CRISPR/Cas9-mediated knockdown normal dysplastic keratinocytes followed increased IL-6 IL-8 secretion, rapid following release from RhoA-activated kinase inhibition. Thus, suggest downregulation early stages process enable development premature deregulated SASP, creating pro-inflammatory state cancer more likely arise.