Signal transducer and activator of transcription 3 upregulates interleukin-8 expression at the level of transcription in human melanoma cells.
Many melanoma cells continuously produce interleukin-8 (IL-8). The involvement of signal transducer and activator of transcription 3 (STAT3) in the constant production of IL-8 in melanoma cells was examined. The level of IL-8 production correlated well with that of the phosphorylated (activated) STAT3 in six human melanoma cell lines. Introduction of the constitutively activated form of STAT3 (STAT3-C) into WM35 melanoma cells, that show low levels of IL-8 and phosphorylated STAT3, enhanced IL-8 production. Knockdown of STAT3 suppressed IL-8 production in WM1205Lu cells that contain a high level of IL-8 accompanied by STAT3 phosphorylation. Introduction of STAT3-C markedly increased the luciferase activity in WM1205Lu cells transfected with reporter vectors linked to the 5'-flanking region of the IL-8 gene from -546 to +44 base pair (bp) and from -272 to +44 bp, but not in cells expressing reporter plasmids from -133 to +44 bp and from -98 to +44 bp. These results indicate that the upregulation of IL-8 production is caused by constitutive STAT3 activation at the level of gene transcription in melanoma cells.
Oka
Masahiro
M
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan. oka@med.kobe-u.ac.jp
Sakaguchi
Masanobu
M
Okada
Taro
T
Nagai
Hiroshi
H
Ozaki
Michitaka
M
Yoshioka
Toyo
T
Inoue
Hiroshi
H
Mukaida
Naofumi
N
Kikkawa
Ushio
U
Nishigori
Chikako
C
D000256:Adenoviridae; D045744:Cell Line, Tumor; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D010957:Plasmids; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology*
D016209:Interleukin-8; D050796:STAT3 Transcription Factor; D008156:Luciferases