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

Takuya Takeichi, Kazumitsu Sugiura, Yoshinao Muro, Kenji Matsumoto, Yasushi Ogawa, Kyoko Futamura, Osamu Kaminuma, Noriko Hashimoto, Yoshie Shimoyama, Hirohisa Saito, Yasushi Tomita

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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 that ectopic expression of LEDGF/DFS70 in KCs could be involved in the pathology of psoriasis vulgaris.

本文言語English
ページ(範囲)2760-2767
ページ数8
ジャーナルJournal of Investigative Dermatology
130
12
DOI
出版ステータスPublished - 12-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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