Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition.
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.
Takeichi
Takuya
T
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Sugiura
Kazumitsu
K
Muro
Yoshinao
Y
Matsumoto
Kenji
K
Ogawa
Yasushi
Y
Futamura
Kyoko
K
Kaminuma
Osamu
O
Hashimoto
Noriko
N
Shimoyama
Yoshie
Y
Saito
Hirohisa
H
Tomita
Yasushi
Y
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D040502:Calgranulin B / Q000235:genetics; D002294:Carcinoma, Squamous Cell; D004817:Epidermis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000091344:Filaggrin Proteins; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D010766:Phosphorylation / Q000502:physiology; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D034741:RNA, Small Interfering; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D040502:Calgranulin B; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D007381:Intermediate Filament Proteins; C504649:PSIP1 protein, human; D034741:RNA, Small Interfering; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D048051:p38 Mitogen-Activated Protein Kinases