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

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 im...

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Autores principales: Fan, Xiaoming, Duan, Qiuhong, Ke, Changshu, Zhang, Guiping, Xiao, Juanjuan, Wu, Dan, Zeng, Xiaoyu, Chen, Jingwen, Guo, Jinguang, Zhou, Jie, Shi, Fei, Zhu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029729/
https://www.ncbi.nlm.nih.gov/pubmed/27016423
http://dx.doi.org/10.18632/oncotarget.8260
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author Fan, Xiaoming
Duan, Qiuhong
Ke, Changshu
Zhang, Guiping
Xiao, Juanjuan
Wu, Dan
Zeng, Xiaoyu
Chen, Jingwen
Guo, Jinguang
Zhou, Jie
Shi, Fei
Zhu, Feng
author_facet Fan, Xiaoming
Duan, Qiuhong
Ke, Changshu
Zhang, Guiping
Xiao, Juanjuan
Wu, Dan
Zeng, Xiaoyu
Chen, Jingwen
Guo, Jinguang
Zhou, Jie
Shi, Fei
Zhu, Feng
author_sort Fan, Xiaoming
collection PubMed
description 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.
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spelling pubmed-50297292016-09-29 Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase Fan, Xiaoming Duan, Qiuhong Ke, Changshu Zhang, Guiping Xiao, Juanjuan Wu, Dan Zeng, Xiaoyu Chen, Jingwen Guo, Jinguang Zhou, Jie Shi, Fei Zhu, Feng Oncotarget Research Paper 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. Impact Journals LLC 2016-03-22 /pmc/articles/PMC5029729/ /pubmed/27016423 http://dx.doi.org/10.18632/oncotarget.8260 Text en Copyright: © 2016 Fan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Fan, Xiaoming
Duan, Qiuhong
Ke, Changshu
Zhang, Guiping
Xiao, Juanjuan
Wu, Dan
Zeng, Xiaoyu
Chen, Jingwen
Guo, Jinguang
Zhou, Jie
Shi, Fei
Zhu, Feng
Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title_full Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title_fullStr Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title_full_unstemmed Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title_short Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase
title_sort cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of t-lak cell-originated protein kinase
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029729/
https://www.ncbi.nlm.nih.gov/pubmed/27016423
http://dx.doi.org/10.18632/oncotarget.8260
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