Research Paper Volume 12, Issue 13 pp 12740—12749
PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells
- 1 Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Jing’an, Shanghai 200072, China
- 2 Department of Critical Care Medicine, The Affiliated Hospital of Medical School of Ningbo, Jiangbei District, Ningbo 315000, Zhejiang province, China
How to Cite
Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human umbilical vein endothelial cells (HUVECs). TNF induces dose- and time-dependent EMP release and downregulation of PAK4 and upstream cdc42 in HUVECs. PAK4 suppression or inhibition of its kinase activity increases TNF-induced EMP release and apoptosis in HUVECs, while PAK4 overexpression reduces EMP release and apoptosis in TNF-stimulated cells. Collectively, these data indicate that PAK4 suppresses TNF-induced EMP generation occurring during apoptosis, and suggest that modulation of PAK4 activity may represent a novel approach to suppress the TNF-induced EMP levels in pro-inflammatory disorders and other pathological conditions.