Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice

Academic Article

Abstract

  • Studies from our laboratory have shown that epigallocatechin-3-gallate, the major polyphenol present in green tea, inhibits ultraviolet (UV)B-exposure-mediated phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl. Pharmacol. 176: 110-117, 2001) and activation of nuclear factor kappa B (NF-κB) (Oncogene 22: 1035-1044, 2003) pathways in normal human epidermal keratinocytes. This study was designed to investigate the relevance of these findings to the in vivo situations in SKH-1 hairless mouse model, which is regarded to have relevance to human situations. SKH-1 hairless mice were topically treated with GTP (5 mg/ 0.2 ml acetone/mouse) and were exposed to UVB 30 min later (180 mJ/cm2). These treatments were repeated every alternate day for 2 weeks, for a total of seven treatments. The animals were killed 24 h after the last UVB exposure. Topical application of GTP resulted in significant decrease in UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes. Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38 protein expression. Since NF-κB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVB-mediated modulations in the NF-κB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-κB, (ii) activation of IKKα, and (iii) phosphorylation and degradation of IκBα. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-κB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system.
  • Published In

  • Oncogene  Journal
  • Digital Object Identifier (doi)

    Author List

  • Afaq F; Ahmad N; Mukhtar H
  • Start Page

  • 9254
  • End Page

  • 9264
  • Volume

  • 22
  • Issue

  • 58