The enhanced IL-18 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT).
Based on our recent observation that enhanced IL-18 expression positively correlates with malignant skin tumors, such as SCC and melanoma, we examined the possible role of UVB, known to be associated with skin cancer development, in the enhancement of IL-18 production using primary human epidermal keratinocytes and human keratinocyte cell line HaCaT. After cells were exposed to UVB irradiation in vitro, IL-18 production was examined by Northern blot analysis and ELISA, and it was found that IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by antioxidant, N-acetyl-L-cysteine (NAC), which suggested the involvement of reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced IL-18 synthesis. We also found that UVB irradiation increased AP-1 binding activity by using EMSA with AP-1-specific oligonucleotide. Furthermore, inhibitors of UVB-induced AP-1 activity, such as PD98059, blocked enhanced IL-18 production, indicating that AP-1 activation is required for UVB-induced IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced IL-18 production is selectively mediated through the generation of ROI and the activation of AP-1.
Cho
Daeho
D
Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Republic of Korea.
Seung Kang
Jae
J
Hoon Park
Jong
J
Kim
Young-In
YI
Hahm
Eunsil
E
Lee
Junechul
J
Yang
Yoolhee
Y
Jeon
Junho
J
Song
Hyunkeun
H
Park
Hyunjeong
H
Kim
Taesung
T
Pang
Saic
S
Kim
Chul-Woo
CW
Il Hwang
Young
Y
Jae Lee
Wang
W
D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation
D020382:Interleukin-18; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1