Elevated ZIPK is required for TNF-α-induced cell adhesion molecule expression and leucocyte adhesion in endothelial cells  

作　　者：Weiwei Zeng Zhiyuan Sun Tengxiang Ma Xiaobin Song Shuai Li Qianqian Zhang Wen Yuan Jing Li Li Liu Minsheng Zhu Huaqun Chen 

机构地区：[1]Jiangsu Key Laboratory for Molecular and Medical Biotechnology,College of Life Sciences,Nanjing Normal University,Nanjing 210023,China [2]Department of Geriatrics,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [3]State Key Laboratory of Pharmaceutical Biotechnology,Medical School of Nanjing University and Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical School,Nanjing University,Nanjing 210008,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第5期567-574,共8页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Natural Science Foundation of China(No.31371356);the Jiangsu Major Nature Science Foundation of High Education(No.13KJA180004);the Priority Academic Program Development of Jiangsu Higher Education Institutions.

摘　　要：Leucocyte adhesion to the vascular endothelium is a critical event in the early inflammatory response to infection and injury.This process is primarily regulated by the expression of cell adhesion molecules(CAMs)in endothelial cells.It has been well documented that tumor necrosis factor alpha(TNF-α)is a key regulator of CAM expression within this process,but its regulatory mechanism remains controversial.To investigate the scenario within this process,we assessed the role of zipper-interacting protein kinase(ZIPK),a serine/threonine kinase with multiple substrates,in CAM expression.We used TNF-αas inflammatory stimulator and found that ZIPK was integrated into the signaling regulation of TNF-α-mediated CAM expression.In human umbilical vein endothelial cells(HUVECs),TNF-αexposure led to significantly increased expression of both intercellular CAM-1(ICAM-1)and vascular CAM-1(VCAM-1),along with an increase in the adhesion of THP-1 monocytes to HUVECs.Simultaneously,ZIPK gene was also up-regulated at the transcription level.These effects were clearly inhibited by the ZIPK-specific inhibitor Tc-DAPK6 or small interfering RNA(siRNA)capable of specifically inhibiting ZIPK expression.We thus suggest that both ZIPK activation and ZIPK gene expression are necessary for TNF-α-mediated CAM expression and leucocyte adhesion.Interestingly,ZIPK inhibition also significantly suppressed TNF-α-induced nuclear factor kappa B(NF-κB)activation,indicating that TNF-α-mediated ZIPK expression functions upstream of NF-κB and CAM expression.We thus propose a TNF-α/ZIPK/NF-κB signaling axis for CAM expression that is necessary for leucocyte adhesion to endothelial cells.Our data in this study revealed a potential molecular target for exploring anti-inflammation drugs.

关 键 词：ZIPK TNF-Α endothelial cells ICAM-1 VCAM-1 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]