Phloroglucinol attenuates ultraviolet B radiation-induced matrix metalloproteinase-1 production in human keratinocytes via inhibitory actions against mitogen-activated protein kinases and activator protein-1

Photochem Photobiol. 2012 Mar-Apr;88(2):381-8. doi: 10.1111/j.1751-1097.2012.01074.x. Epub 2012 Jan 25.

Abstract

Excessive amounts of reactive oxygen species (ROS) induced by ultraviolet (UV) radiation cause skin aging via basement membrane/extracellular matrix degradation resulting from the action of matrix metalloproteinases (MMPs). Recently, phloroglucinol (1,3,5-trihydroxybenzene) was demonstrated to attenuate the cell damage induced by oxidative stress by quenching ROS and stimulating antioxidant systems. In the current study, the effect of phloroglucinol on UVB-induced photoaging was investigated in human HaCaT keratinocytes. Phloroglucinol significantly inhibited the UVB-induced (1) upregulation of MMP-1 mRNA, protein and activity; (2) augmentation of intracellular Ca(2+) levels; (3) phosphorylation of mitogen-activated protein kinases (MAPKs); (4) expression of c-Fos and phospho c-Jun; and (5) enhancement of activator protein-1 (AP-1) binding to the MMP-1 promoter. In addition, the knockdown of MAPKs significantly inhibited UVB-induced MMP-1 expression. The results of this study suggest that phloroglucinol may be useful as a photoprotective compound for the skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Gene Expression* / drug effects
  • Gene Expression* / radiation effects
  • Gene Knockdown Techniques
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase Inhibitors*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / genetics
  • Oxidative Stress
  • Phloroglucinol* / pharmacology
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / antagonists & inhibitors
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Skin / drug effects
  • Skin / radiation effects
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / genetics
  • Ultraviolet Rays / adverse effects*

Substances

  • Matrix Metalloproteinase Inhibitors
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • Phloroglucinol
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 1
  • Calcium