Hsu Stephen, Dickinson Douglas, Borke James, Walsh Douglas S, Wood Joseph, Qin Haiyan, Winger Julia, Pearl Henna, Schuster George, Bollag Wendy B
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, GA 30912, USA.
Exp Dermatol. 2007 Aug;16(8):678-84. doi: 10.1111/j.1600-0625.2007.00585.x.
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.
银屑病样病变的特征是表皮角质形成细胞过度增殖和异常分化，并伴有炎症，导致皮肤屏障破坏和角质层异常。半胱天冬酶14是半胱天冬酶家族的成员，与上皮细胞分化、程序性细胞死亡和屏障形成有关，其表达和蛋白水解加工在银屑病表皮中发生改变。我们最近报道，人类银屑病组织缺乏半胱天冬酶14的正常表达[《皮肤病学杂志》37(2005)61]，并且在指数生长的正常人表皮角质形成细胞(NHEK)中，表没食子儿茶素没食子酸酯(EGCG，一种绿茶多酚(GTP))可诱导半胱天冬酶14表达[《药理学与实验治疗学杂志》315(2005)805]。这表明GTP可能对银屑病样病变有有益作用。本研究旨在确定NHEK中GTP诱导的半胱天冬酶14表达是否需要丝裂原活化蛋白激酶(MAPK)途径，以及GTP是否能调节片状皮肤小鼠发生的银屑病样病变中病理标志物的表达。结果表明，p38和JNK MAPK途径是EGCG诱导NHEK中半胱天冬酶14表达所必需的。重要的是，局部应用0.5% GTP可显著减轻片状皮肤小鼠的表皮病理症状，这与有效的半胱天冬酶14加工和增殖细胞核抗原水平降低有关。这表明GTP激活的途径可能是治疗某些银屑病样皮肤疾病新治疗方法的潜在靶点。
