5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells

Jae Kyung Kim, Sukyeong Mun, Myung Suk Kim, Mi Bo Kim, Bo Kyung Sa, Jae Kwan Hwang

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR α, δ and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-κB). We evaluated the ability of the PPARα/γ activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARα/γ expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-κB signalling were evaluated by Western blot analysis. PPARα/γ activity was assessed with the GAL4/PPARα/γ transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARα/γ activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced IκBα phosphorylation, blocked NF-κB p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-κB and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalExperimental dermatology
Volume21
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

Fingerprint

Peroxisome Proliferator-Activated Receptors
Fibroblasts
Matrix Metalloproteinases
Skin
Cells
NF-kappa B
Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Catalase
Assays
Reactive Oxygen Species
Transcription Factors
Cytokines
Inflammation
Skin Aging
5,7-dimethoxyflavone
Immunosorbents
Phosphorylation
Oxidative stress
Polymerase chain reaction

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Kim, Jae Kyung ; Mun, Sukyeong ; Kim, Myung Suk ; Kim, Mi Bo ; Sa, Bo Kyung ; Hwang, Jae Kwan. / 5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells. In: Experimental dermatology. 2012 ; Vol. 21, No. 3. pp. 211-216.
@article{f207b84c965e43d3a07e0f5cfe4a862f,
title = "5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells",
abstract = "Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR α, δ and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-κB). We evaluated the ability of the PPARα/γ activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARα/γ expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-κB signalling were evaluated by Western blot analysis. PPARα/γ activity was assessed with the GAL4/PPARα/γ transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARα/γ activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced IκBα phosphorylation, blocked NF-κB p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-κB and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.",
author = "Kim, {Jae Kyung} and Sukyeong Mun and Kim, {Myung Suk} and Kim, {Mi Bo} and Sa, {Bo Kyung} and Hwang, {Jae Kwan}",
year = "2012",
month = "3",
day = "1",
doi = "10.1111/j.1600-0625.2011.01435.x",
language = "English",
volume = "21",
pages = "211--216",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "3",

}

5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells. / Kim, Jae Kyung; Mun, Sukyeong; Kim, Myung Suk; Kim, Mi Bo; Sa, Bo Kyung; Hwang, Jae Kwan.

In: Experimental dermatology, Vol. 21, No. 3, 01.03.2012, p. 211-216.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells

AU - Kim, Jae Kyung

AU - Mun, Sukyeong

AU - Kim, Myung Suk

AU - Kim, Mi Bo

AU - Sa, Bo Kyung

AU - Hwang, Jae Kwan

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR α, δ and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-κB). We evaluated the ability of the PPARα/γ activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARα/γ expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-κB signalling were evaluated by Western blot analysis. PPARα/γ activity was assessed with the GAL4/PPARα/γ transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARα/γ activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced IκBα phosphorylation, blocked NF-κB p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-κB and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.

AB - Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR α, δ and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-κB). We evaluated the ability of the PPARα/γ activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARα/γ expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-κB signalling were evaluated by Western blot analysis. PPARα/γ activity was assessed with the GAL4/PPARα/γ transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARα/γ activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced IκBα phosphorylation, blocked NF-κB p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-κB and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.

UR - http://www.scopus.com/inward/record.url?scp=84863284578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863284578&partnerID=8YFLogxK

U2 - 10.1111/j.1600-0625.2011.01435.x

DO - 10.1111/j.1600-0625.2011.01435.x

M3 - Article

C2 - 22379967

AN - SCOPUS:84863284578

VL - 21

SP - 211

EP - 216

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 3

ER -