1. Academic Validation
  2. Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase

Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase

  • Oncotarget. 2016 Apr 26;7(17):24633-45. doi: 10.18632/oncotarget.8260.
Xiaoming Fan 1 Qiuhong Duan 1 Changshu Ke 2 Guiping Zhang 3 Juanjuan Xiao 1 Dan Wu 1 Xiaoyu Zeng 1 Jingwen Chen 4 Jinguang Guo 4 Jie Zhou 1 Fei Shi 4 Feng Zhu 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
  • 2 Department of Pathology, Tongji hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
  • 3 Shanghai Biyi Chemical Science and Technology Co., Shanghai, 201203, PR China.
  • 4 Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.
Abstract

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-α 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-α 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.

Keywords

TOPK; cefradine; signal transduction pathway; skin inflammation; solar UV.

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