Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

Diabetologia
Kleber L A SouzaM Tiedge

Abstract

Cytokines are important humoral mediators of beta cell destruction in autoimmune diabetes. The aim of this study was to identify novel cytokine-induced genes in insulin-producing RINm5F cells, which may contribute to beta cell death or survival. A global gene expression profile in cytokine-exposed insulin-producing RINm5F cells was achieved by automated restriction fragment differential display PCR. The expression of selected candidate genes was confirmed by real-time RT-PCR analysis. Exposure of RINm5F cells to IL-1beta or to a cytokine mixture (IL-1beta, TNF-alpha, IFN-gamma) for 6 h resulted in the differential expression of a functional gene cluster. Apart from the well-known up-regulation of the cytokine-responsive genes iNOS, NF-kappaB, MnSOD and Hsp70, several genes that belong to the functional cluster of the endocytotic pathway were identified. These endocytotic genes comprised: clathrin, megalin, synaptotagmin and calcineurin, which were up-regulated by IL-1beta or the cytokine mixture. In contrast, the expression of the calcineurin inhibitor CAIN and of the GDP/GTP exchange protein Rab3 was down-regulated by cytokines. Other up-regulated cytokine-responsive genes were: agrin, murine adherent macrophage protein mRNA (...Continue Reading

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Citations

Sep 6, 2011·Redox Report : Communications in Free Radical Research·Letícia P RomaKleber L A Souza
Sep 6, 2013·Biochimica Et Biophysica Acta·Srividya VasuPeter R Flatt
Jun 2, 2017·Physiological Reviews·Nicholas StaffordElizabeth J Cartwright
Apr 29, 2005·Diabetes/metabolism Research and Reviews
Dec 21, 2014·Journal of Molecular Endocrinology·Srividya VasuPeter R Flatt
Jul 14, 2010·Molecular and Cellular Biochemistry·Blanca Delgado-CoelloJaime Mas-Oliva

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