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

Biochem Biophys Res Commun. 2009 Sep 11;387(1):115-20. doi: 10.1016/j.bbrc.2009.06.137. Epub 2009 Jul 1.

Abstract

Keratinocytes, one of major cell types in the skin, can 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-kappaB 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 anti-inflammatory responses by suppressing TNF-alpha and/or IFN-gamma-induced activation of NF-kappaB and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Chemokine CCL17 / biosynthesis*
  • Humans
  • Hydrolyzable Tannins / pharmacology*
  • Interferon-gamma / pharmacology
  • Juglans / chemistry
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • NF-kappa B / metabolism*
  • STAT1 Transcription Factor / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • CCL17 protein, human
  • Chemokine CCL17
  • Hydrolyzable Tannins
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tumor Necrosis Factor-alpha
  • pentagalloylglucose
  • Interferon-gamma