Tumor necrosis factor alpha inhibits transcriptional activity of the porcine P-45011A insulin-like growth factor response element.

The Journal of Biological Chemistry
R J UrbanY Bodenburg

Abstract

We investigated the effects of tumor necrosis factor alpha (TNFalpha) on the transcriptional activity of the porcine P-45011A (P450scc) insulin-like growth factor response element (IGFRE). TNFalpha inhibited insulin-like growth factor-I (IGF-I)-stimulated P450scc mRNA concentrations in cultures of porcine granulosa cells. Transient transfection experiments in granulosa cells with deletion P450scc/luciferase constructs showed that TNFalpha inhibited the transcriptional activity of the IGFRE. IGF-I binding and IGF-I receptor mRNA concentrations in porcine granulosa cells were not inhibited by TNFalpha. Electrophoretic mobility shift assay with nuclear extract protein from porcine granulosa cells treated with IGF-I and TNFalpha showed that Sp1 and a second transcription factor, P2, bound to the IGFRE. While IGF-I treatment increased the binding activity of both factors, TNFalpha specifically inhibited the IGF-I-stimulated binding activity of P2. Transient transfection studies done in mouse fibroblasts overexpressing the IGF-I receptor (NWTb3) with the porcine IGFRE (three repeats) in an SV40/luciferase construct also showed TNFalpha inhibited IGF-I-stimulated reporter gene expression. We conclude that TNFalpha inhibits the transcr...Continue Reading

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Citations

Dec 7, 2007·American Journal of Physiology. Endocrinology and Metabolism·Sekar NatesampillaiJohannes D Veldhuis
Sep 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Randall J Urban, Yvonne Bodenburg
Jan 30, 2004·American Journal of Physiology. Endocrinology and Metabolism·Randall J UrbanJorge Chedrese
Aug 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Randall J UrbanThomas G Wood

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