Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition

The Journal of Investigative Dermatology
Takuya TakeichiYasushi Tomita

Abstract

Lens epithelium-derived growth factor (LEDGF)/dense fine speckles 70  kDa protein (DFS70) is a transcription cofactor that enhances growth and is overexpressed in various cancers. In the epidermis, LEDGF/DFS70 localizes to the nucleus of keratinocytes (KCs) in the basal layers and to the cytoplasm of cells in the upper layers. However, the biological and pathological relevance of LEDGF/DFS70 in the epidermis is virtually unknown. Compared with normal epidermis, we detected strong nuclear staining of LEDGF/DFS70 in both the spinous and basal layers of the epidermis of psoriatic skin. To investigate the roles of LEDGF/DFS70 in the epidermis of psoriatic skin, we generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP)-LEDGF (EGFP-LEDGF-HaCaT) or EGFP alone (EGFP-HaCaT) as a control. EGFP-LEDGF-HaCaT cells had increased expression of IL-6, which was attenuated by LEDGF-specific RNA interference and the p38-specific inhibitors SB-239063 and SB-203580. Furthermore, EGFP-LEDGF-HaCaT cells had increased expression of S100A7 and S100A9 and decreased expression of filaggrin. These findings are compatible with the expression pattern in psoriatic tissues. Taken together, these results strongly suggest t...Continue Reading

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Citations

Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Francesca ZammarchiLuca Cartegni
Oct 25, 2011·Journal of Molecular Biology·Sébastien DesfargesAngela Ciuffi
Jun 17, 2011·Journal of Dermatological Science·Takuya TakeichiMasashi Akiyama
Dec 29, 2015·The Journal of Pharmacy and Pharmacology·Florian Guenther, Matthias F Melzig
Nov 10, 2011·Cellular & Molecular Biology Letters·Stina K Carlsson, J Peter Gierow
Jul 2, 2014·The International Journal of Biochemistry & Cell Biology·Wenyan SunJiankang Liu
Aug 14, 2012·Experimental Dermatology·Claus KerkhoffKarin E Bornfeldt
Jan 12, 2011·Archives of Dermatological Research·Michiko HibinoYasushi Tomita
Dec 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joan DefrênePhilippe A Tessier

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