Sargahydroquinoic acid inhibits TNF alpha-induced AP-1 and NF-kappa B signaling in HaCaT cells through PPAR alpha 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 PPAR alpha/gamma functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NE-kappa B). However, the detailed mechanism of PPAR alpha/gamma's role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPAR alpha/gamma ligand significantly decreased Tumor Necrosis Factor-alpha (TNF alpha)-induced MMP-2/-9 expression by downregulating TNF alpha-induced transcription factors, subsequently reducing I kappa B alpha degradation and blocking NE-kappa B p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPAR alpha antagonist) not bisphenol A diglycidyl ether (PPAR gamma antagonists), reversed the effect on TNF alpha-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNF alpha-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NE-kappa B pathway via PPAR alpha. (C) 2014 Elsevier Inc. All rights reserved.