Skin inflammation, and skin cancer induced by excessive solar ultraviolet (SUV) is a great threat to human health. SUV induced skin inflammation through activating p38 mitogen-activated protein kinase (p38) and c-Jun N-termeinal kinases (JNKs). T-LAK cell-originated protein kinase (TOPK) plays an important role in this process. Herein, the clinical data showed TOPK, phospho-p38, phospho-JNKs were highly expressed in human solar dermatitis. Ex vivo studies showed that SUV induced the phosphorylation of p38 and JNKs in HaCat and JB6 cells in a dose and time dependent manner. Molecule docking model indicated cefradine, an FDA-approved cephalosporin antibiotic, directly binds with TOPK. The result of in vitro binding assay verified cefradine can directly bind with TOPK. In vitro kinase results showed cefradine can inhibit TOPK activity. Ex vivo studies further showed cefradine inhibited SUV-induced the phosphorylation level of p38, JNKs and H2AX through inhibiting TOPK activity in a dose and time dependent manner, and cefradine inhibited the secretion of IL6 and TNF-alpha in HaCat and JB6 cells. In vivo studies showed that cefradine down-regulated SUV-induced the phosphorylation of p38, JNKs and H2AX and inhibited the secretion of IL6 and TNF-alpha in Babl/c mice. These results indicated that cefradine can inhibit SUV-induced skin inflammation by blocking TOPK signaling pathway, and TOPK is an effective target for suppressing inflammation induced by SUV irradiation.
基金：
National Natural Science Foundation of China [81472602, 81450110449, 81250004]; Independent innovation project of Huazhong University of Science and Technology [2014TS063, 2015650011, 2014ZZGH013]; Natural Science Foundation of Hubei Province [2014CFB447]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430030, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Fan Xiaoming,Duan Qiuhong,Ke Changshu,et al.Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase[J].ONCOTARGET.2016,7(17):24633-24645.doi:10.18632/oncotarget.8260.
APA：
Fan, Xiaoming,Duan, Qiuhong,Ke, Changshu,Zhang, Guiping,Xiao, Juanjuan...&Zhu, Feng.(2016).Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase.ONCOTARGET,7,(17)
MLA：
Fan, Xiaoming,et al."Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase".ONCOTARGET 7..17(2016):24633-24645
医学