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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)2760-2767
Number of pages8
JournalJournal of Investigative Dermatology
Volume130
Issue number12
DOIs
Publication statusPublished - 12-2010

Fingerprint

Speckle
Interleukin-6
Chemical activation
Epidermis
Proteins
Fluorescence
Keratinocytes
Skin
lens epithelium-derived growth factor
Pathology
Transcription
RNA Interference
Psoriasis
Cytoplasm
RNA
Tissue
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Takeichi, Takuya ; Sugiura, Kazumitsu ; Muro, Yoshinao ; Matsumoto, Kenji ; Ogawa, Yasushi ; Futamura, Kyoko ; Kaminuma, Osamu ; Hashimoto, Noriko ; Shimoyama, Yoshie ; Saito, Hirohisa ; Tomita, Yasushi. / Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 12. pp. 2760-2767.
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title = "Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition",
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 that ectopic expression of LEDGF/DFS70 in KCs could be involved in the pathology of psoriasis vulgaris.",
author = "Takuya Takeichi and Kazumitsu Sugiura and Yoshinao Muro and Kenji Matsumoto and Yasushi Ogawa and Kyoko Futamura and Osamu Kaminuma and Noriko Hashimoto and Yoshie Shimoyama and Hirohisa Saito and Yasushi Tomita",
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Takeichi, T, Sugiura, K, Muro, Y, Matsumoto, K, Ogawa, Y, Futamura, K, Kaminuma, O, Hashimoto, N, Shimoyama, Y, Saito, H & Tomita, Y 2010, 'Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition', Journal of Investigative Dermatology, vol. 130, no. 12, pp. 2760-2767. https://doi.org/10.1038/jid.2010.203

Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition. / Takeichi, Takuya; Sugiura, Kazumitsu; Muro, Yoshinao; Matsumoto, Kenji; Ogawa, Yasushi; Futamura, Kyoko; Kaminuma, Osamu; Hashimoto, Noriko; Shimoyama, Yoshie; Saito, Hirohisa; Tomita, Yasushi.

In: Journal of Investigative Dermatology, Vol. 130, No. 12, 12.2010, p. 2760-2767.

Research output: Contribution to journalArticle

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T1 - Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition

AU - Takeichi, Takuya

AU - Sugiura, Kazumitsu

AU - Muro, Yoshinao

AU - Matsumoto, Kenji

AU - Ogawa, Yasushi

AU - Futamura, Kyoko

AU - Kaminuma, Osamu

AU - Hashimoto, Noriko

AU - Shimoyama, Yoshie

AU - Saito, Hirohisa

AU - Tomita, Yasushi

PY - 2010/12

Y1 - 2010/12

N2 - 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.

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