UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species

Ho Cheol Ryu, Cheolmin Kim, Joo Young Kim, Jin Ho Chung, Jae-Hong Kim

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B 4 receptor, and its ligands (LTB 4 and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a BLT2-Nox1-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.

Original languageEnglish
Pages (from-to)1095-1106
Number of pages12
JournalJournal of Investigative Dermatology
Volume130
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1

Fingerprint

Keratinocytes
Reactive Oxygen Species
LY 255283
Radiation
Apoptosis
Skin
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Irradiation
Sunburn
Leukotriene B4
NADPH Oxidase
Cell death
Transgenic Mice
Cell Death
Ligands
Proteins

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species. / Ryu, Ho Cheol; Kim, Cheolmin; Kim, Joo Young; Chung, Jin Ho; Kim, Jae-Hong.

In: Journal of Investigative Dermatology, Vol. 130, No. 4, 01.04.2010, p. 1095-1106.

Research output: Contribution to journalArticle

Ryu, Ho Cheol ; Kim, Cheolmin ; Kim, Joo Young ; Chung, Jin Ho ; Kim, Jae-Hong. / UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 4. pp. 1095-1106.
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