Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells.
10.3858/emm.2010.42.12.086
- Author:
Cheolmin KIM
1
;
Ho Cheol RYU
;
Jae Hong KIM
Author Information
1. College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. jhongkim@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
12-hydroxy-5,8,10,14-eicosatetraenoic acid;
leukotriene B4;
LTB4R2 protein, human;
matrix metalloproteinase 1;
reactive oxygen species;
skin aging;
ultraviolet rays
- MeSH:
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/biosynthesis;
Cell Line;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Humans;
Keratinocytes/metabolism/*radiation effects;
Leukotriene B4/biosynthesis;
Matrix Metalloproteinase 1/*biosynthesis;
Phosphorylation;
Reactive Oxygen Species/metabolism;
Receptors, Leukotriene B4/*physiology;
Signal Transduction;
Ultraviolet Rays/*adverse effects
- From:Experimental & Molecular Medicine
2010;42(12):833-841
- CountryRepublic of Korea
- Language:English
-
Abstract:
Skin exposure to low-dose ultraviolet B (UVB) light up-regulates the expression of matrix metalloproteinase-1 (MMP-1), thus contributing to premature skin aging (photo-aging). Although cyclooxygenase-2 (COX-2) and its product, prostaglandin E2 (PGE2), have been associated with UVB-induced signaling to MMP expression, very little are known about the roles of lipoxygenases and their products, especially leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), in MMP-1 expression in skin keratinocytes. In the present study, we demonstrate that BLT2, a cell surface receptor for LTB4 and 12(S)-HETE, plays a critical role in UVB-mediated MMP-1 upregulation in human HaCaT keratinocytes. Moreover, our results demonstrated that BLT2-mediated MMP-1 upregulation occurs through a signaling pathway dependent on reactive oxygen species (ROS) production and the subsequent stimulation of ERK. Blockage of BLT2 via siRNA knockdown or with the BLT2-antagonist LY255283 completely abolished the up-regulated expression of MMP-1 induced by low-dose UVB irradiation. Finally, when HaCaT cells were transiently transfected with a BLT2 expression plasmid, MMP-1 expression was significantly enhanced, along with ERK phosphorylation, suggesting that BLT2 overexpression alone is sufficient for MMP-1 up-regulation. Together, our results suggest that the BLT2-ROS-ERK-linked cascade is a novel signaling mechanism for MMP-1 upregulation in low-dose UVB-irradiated keratinocytes and thus potentially contributes to photo-aging.
