Title |
IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene
|
---|---|
Published in |
Frontiers in Cell and Developmental Biology, February 2018
|
DOI | 10.3389/fcell.2018.00007 |
Pubmed ID | |
Authors |
Dhivya Thiyagarajan, Hege L. Pedersen, Natalya Seredkina, Kjersti D. Horvei, Lorena Arranz, Ramon Sonneveld, Tom Nijenhuis, Johan van der Vlag, Ole P. Rekvig |
Abstract |
Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR and western blot analyses, in presence or absence of siRNA against IL-1β and DNase I mRNA. Nuclear DNase I bound to theFASpromotor region as determined by chromatin immuno-precipitation analysis. Data demonstrate that; (i) translocation of DNase I depended on endogenousde novo-expressed IL-1β, (ii) nuclear DNase I boundFASDNA, (iii) FasR expression increased after translocation of DNase I, (iv) interaction ofexogenousFas ligand (FasL) with upregulated FasR induced apoptosis in human tubular cells stimulated with TNFα. Thus, translocated DNase I most probably binds the promoter region of theFASgene and function as a transcription factor for FasR. In conclusion, DNase I not only executes chromatin degradationduringapoptosis and necrosis, but also primes the cellsforapoptosis by enhancing FasR expression. |
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