Exp Mol Med.  2010 Dec;42(12):833-841. 10.3858/emm.2010.42.12.086.

Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells

• Kim C
• Ryu HC
• Kim JH

• KMID: 1115267
• DOI: http://doi.org/10.3858/emm.2010.42.12.086

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.

Keyword

12-hydroxy-5,8,10,14-eicosatetraenoic acid; leukotriene B4; LTB4R2 protein, human; matrix metalloproteinase 1; reactive oxygen species; skin aging; ultraviolet rays

MeSH Terms

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