The effect of cilostazol on the expression of matrix metalloproteinase-1 and type I procollagen in ultraviolet-irradiated human dermal fibroblasts

Life Sci. 2013 Mar 12;92(4-5):282-8. doi: 10.1016/j.lfs.2012.12.011. Epub 2013 Jan 16.

Abstract

Aim: Cilostazol is a selective inhibitor of type III phosphodiesterase that inhibits platelet aggregation. Cilostazol is a useful vasodilator, antithrombotic, and cardiotonic agent. Ultraviolet B (UVB) irradiation increases the production of matrix metalloproteinase-1 (MMP-1) during skin photoaging. The UVB-induced increase of MMP-1 results in connective tissue damage, and the skin becomes wrinkled and aged. Here, we investigated the capacity of cilostazol to inhibit MMP-1 expression in UVB-irradiated human dermal fibroblasts.

Main methods: Cultured human dermal fibroblasts were irradiated with UVB, followed by the addition of cilostazol to the culture medium.

Key findings: Post-treatment with cilostazol attenuated UVB-induced production of MMP-1 and prevented the reduction of type I procollagen. Cilostazol inhibited UVB irradiation-induced phosphorylation of the mitogen-activated protein kinase (MAPK) signaling molecules Jun-N-terminal kinase (JNK) and p38 kinase, as well as activator protein-1 (AP-1) in dermal fibroblasts.

Significance: Overall, these results demonstrate that cilostazol regulates UVB-induced MMP-1 expression and type I procollagen synthesis by inhibiting MAPK signaling and AP-1 activity. Therefore, we suggest that cilostazol may be useful for the prevention and treatment of skin photodamage caused by UVB-irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Cilostazol
  • Collagen Type I / biosynthesis*
  • Electrophoretic Mobility Shift Assay
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Molecular Structure
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / radiation effects
  • Skin Aging / drug effects
  • Skin Aging / radiation effects
  • Sunscreening Agents / pharmacology
  • Tetrazoles / pharmacology*
  • Transcription Factor AP-1 / metabolism
  • Ultraviolet Rays*

Substances

  • Collagen Type I
  • Reactive Oxygen Species
  • Sunscreening Agents
  • Tetrazoles
  • Transcription Factor AP-1
  • MMP1 protein, human
  • Matrix Metalloproteinase 1
  • Cilostazol