Sargahydroquinoic acid inhibits TNFalpha-induced AP-1 and NF-kappaB signaling in HaCaT cells through PPARalpha activation.
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Jeon Y, Jung Y, Kim MC, Kwon HC, Kang KS, Kim YK, Kim SN
Sargahydroquinoic acid inhibits TNFalpha-induced AP-1 and NF-kappaB signaling in HaCaT cells through PPARalpha activation.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1553-9. doi: 10.1016/j.bbrc.2014.07.026. Epub 2014 Jul 11.
- PubMed ID
- 25019995 [ View in PubMed]
- 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 PPARalpha/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 (NF-kappaB). However, the detailed mechanism of PPARalpha/gamma's role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARalpha/gamma ligand significantly decreased Tumor Necrosis Factor-alpha (TNFalpha)-induced MMP-2/-9 expression by downregulating TNFalpha-induced transcription factors, subsequently reducing IkappaBalpha degradation and blocking NF-kappaB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARalpha antagonist) not bisphenol A diglycidyl ether (PPARgamma antagonists), reversed the effect on TNFalpha-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFalpha-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-kappaB pathway via PPARalpha.