title: The enhanced IL-18 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT).
abstract: 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.
authors.affiliation: Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Republic of Korea.
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Jae
authors.initials: J
authors.lastname: Seung Kang
authors.forename: Jong
authors.initials: J
authors.lastname: Hoon Park
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kim
authors.forename: Eunsil
authors.initials: E
authors.lastname: Hahm
authors.forename: Junechul
authors.initials: J
authors.lastname: Lee
authors.forename: Yoolhee
authors.initials: Y
authors.lastname: Yang
authors.forename: Junho
authors.initials: J
authors.lastname: Jeon
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Park
authors.forename: Taesung
authors.initials: T
authors.lastname: Kim
authors.forename: Saic
authors.initials: S
authors.lastname: Pang
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Il Hwang
authors.forename: Wang
authors.initials: W
authors.lastname: Jae Lee
mesh_terms: 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
chemical_list: D020382:Interleukin-18; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1