Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-β-D-glucose via blockade of NF-κB and STAT1 activation in the HaCaT cells

Keratinocytes, one of major cell types in the skin, call be induced by TNF-alpha and IFN-gamma to express thymus- and activation-regulated chemokine (TARC/CCL17), which is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, Such as atopic dermatitis (AD). In this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), isolated from the barks of Juglans mandshurica, on TNF-alpha/IFN-gamma induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment of HaCaT cells with PGG suppressed TNF-alpha/iFN-gamma-induced protein and mRNA expression of CCL17. PGG significantly inhibited TNF-alpha/IFN-gamma-induced NF-kappa B activation as well as STAT1 activation. Furthermore, pretreatment with PGG resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT cells treated with IFN-gamma. These results suggest that PGG may exert antiinflammatory responses by suppressing TNF-alpha and/or IFN-gamma-induced activation of NF-kappa B and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases. (C) 2009 Elsevier Inc. All rights reserved.