Sargahydroquinoic acid inhibits TNFα-induced AP-1 and NF-κB signaling in HaCaT cells through PPARα activation.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γ's role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.

• Authors: Youngsic Jeon, Yujung Jung, Min Cheol Kim, Hak Cheol Kwon, Ki Sung Kang, Yong Kee Kim, Su-Nam Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 450 Issue 4 Pg. 1553-9 (Aug 08 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25019995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Alkenes
• Benzoquinones
• DNA Primers
• NF-kappa B
• PPAR alpha
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• sargahydroquinoic acid

Topics

• Alkenes (pharmacology)
• Base Sequence
• Benzoquinones (pharmacology)
• Cell Line
• DNA Primers
• Humans
• NF-kappa B (metabolism)
• PPAR alpha (agonists)
• Phosphorylation
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (metabolism)
• Tumor Necrosis Factor-alpha (physiology)