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-ROSROSERK- linked cascade is a novel signaling mechanism for MMP-1 upregulation in low-dose UVB- irradiated keratinocytes and thus potentially contributes to photo- aging.
Original language | English |
---|---|
Pages (from-to) | 833-841 |
Number of pages | 9 |
Journal | Experimental and Molecular Medicine |
Volume | 42 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2010 Dec |
Keywords
- 10
- 12-hydroxy-5
- 14-eicosatetraenoic acid
- 8
- Human
- Matrix metalloproteinase 1
- Reactive oxygen species
- Skin aging
- Ultraviolet rays
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry