title: Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model.
abstract: Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. The expression and proteolytic processing of caspase 14, a member of the caspase family which is associated with epithelial cell differentiation, planned cell death, and barrier formation, is altered in psoriatic epidermis. We recently reported that human psoriatic tissues lack normal expression of caspase 14 [J Dermatol Sci37 (2005) 61], and caspase 14 is induced by EGCG, a green tea polyphenol (GTP), in exponentially growing normal human epidermal keratinocytes (NHEK) [J Pharmacol Exp Ther315 (2005) 805]. This suggests that GTPs may have beneficial effects on psoriasiform lesions. The current study aimed to determine whether MAPK pathways are required for GTP-induced caspase 14 expression in NHEK and if GTPs can modulate the expression of pathological markers in the psoriasiform lesions that develop in the flaky skin mouse. The results indicate that the p38 and JNK MAPK pathways are required for EGCG-induced expression of caspase 14 in NHEK. Importantly, topical application of 0.5% GTPs significantly reduced the symptoms of epidermal pathology in the flaky skin mice, associated with efficient caspase 14 processing and reduction in proliferating cell nuclear antigen levels. This suggests that GTP-activated pathways may be potential targets for novel therapeutic approaches to the treatment of some psoriasiform skin disorders.
authors.affiliation: Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, GA 30912, USA. shsu@mail.mcg.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Hsu
authors.forename: Douglas
authors.initials: D
authors.lastname: Dickinson
authors.forename: James
authors.initials: J
authors.lastname: Borke
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Walsh
authors.forename: Joseph
authors.initials: J
authors.lastname: Wood
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qin
authors.forename: Julia
authors.initials: J
authors.lastname: Winger
authors.forename: Henna
authors.initials: H
authors.lastname: Pearl
authors.forename: George
authors.initials: G
authors.lastname: Schuster
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
mesh_terms: D000818:Animals; D053456:Caspase 14 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012468:Salivary Gland Neoplasms; D013662:Tea; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C506449:Casp14 protein, mouse; D053456:Caspase 14; D020169:Caspases