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Adhesion and migration of inflammatory leukocytes into tissues is a crucial process in the pathogenesis of various inflammatory diseases. Tumor necrosis factor α (TNF-α) is a key proinflammatory cytokine that mediates transendothelial migration of inflammatory cells. The small GTP-binding protein Rab11a plays a key role in the modulation of receptor-mediated endocytosis. However, the expression and function of Rab11a in vascular endothelial cells (VECs) remains to be defined. Here we show that TNF-α upregulates Rab11a expression in cultured human umbilical vein endothelial cells (HUVECs). TNF-α-mediated Rab11a upregulation is dependent on the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Pharmacological inhibition of p38 MAPK signaling and overexpression of Rab11a siRNA markedly suppress TNF-α-induced adhesion and migration of leukocytes to VECs. Moreover, p38 MAPK activation is found to enhance the expression of Rab11a in VECs. Our results suggest that p38 MAPK signaling pathway, which is activated by TNF-α, is involved in the upregulation of Rab11a in VECs and that Rab11a may contribute to enhanced leukocyte-endothelial interaction in inflamed vessels.Irish wine has a reputation of being cheaper and worse than it really is. The fact that it's better than most other wine brands is a bonus but the reputation is fair enough - there are few wines that are cheaper than a bottle of Irish whiskey. But is the drink in fact bad? You have to ask, does it live up to the hype?
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