title: Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice.
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-kappaB) (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-kappaB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVB-mediated modulations in the NF-kappaB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-kappaB, (ii) activation of IKKalpha, and (iii) phosphorylation and degradation of IkappaBalpha. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-kappaB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system.
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Afaq
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004487:Edema / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006965:Hyperplasia; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013662:Tea; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D000072000:NF-KappaB Inhibitor alpha; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D020928:Mitogen-Activated Protein Kinases