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.
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.
Jeju National University School of Medicine and Applied Radiological Science Research Institute, Jeju, South Korea.
Mei Jing
MJ
Piao
Rui
R
Zhang
Nam Ho
NH
Lee
Jin Won
JW
Hyun
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D018384:Oxidative Stress; D010696:Phloroglucinol / Q000494:pharmacology; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
D061965:Matrix Metalloproteinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D010696:Phloroglucinol; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; D002118:Calcium