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

Cheolmin Kim, Ho Cheol Ryu, Jae-Hong Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 languageEnglish
Pages (from-to)833-841
Number of pages9
JournalExperimental and Molecular Medicine
Volume42
Issue number12
DOIs
Publication statusPublished - 2010 Dec 1

Fingerprint

Matrix Metalloproteinase 1
Dosimetry
Irradiation
Up-Regulation
Leukotriene B4
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Keratinocytes
Skin
Aging of materials
LY 255283
Lipoxygenases
Premature Aging
Skin Aging
Phosphorylation
Cell Surface Receptors
Cyclooxygenase 2
Ultraviolet Rays
Matrix Metalloproteinases
Dinoprostone
Small Interfering RNA

Keywords

  • 10
  • 12-hydroxy-5
  • 14-eicosatetraenoic acid
  • 8
  • Human
  • Leukotriene B
  • LTBR2 protein
  • Matrix metalloproteinase 1
  • Reactive oxygen species
  • Skin aging
  • Ultraviolet rays

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells. / Kim, Cheolmin; Ryu, Ho Cheol; Kim, Jae-Hong.

In: Experimental and Molecular Medicine, Vol. 42, No. 12, 01.12.2010, p. 833-841.

Research output: Contribution to journalArticle

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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.",
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