CYCLIC STRETCH UP-REGULATES PRODUCTION OF INTERLEUKIN-8 AND MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN HUMAN ENDOTHELIAL-CELLS

In vivo, vascular walls are exposed to mechanical stretch, which may p romote atherogenesis. This study was designed to investigate the effec t of mechanical stretch on the production and gene expression of cytok ines in endothelial cells (ECs) of human umbilical veins. ECs were cul tured on flexible silicone membranes and exposed to cyclic mechanical stretch. Although the secretion levels of interleukin (IL)-1 beta, tum or necrosis factor-alpha, IL-6, granulocyte (G) -colony stimulating fa ctor(CSF), G and macrophage (M) -CSF, and M-CSF were not affected by c yclic stretch over 24 hours, the levels of IL-8 and monocyte chemotact ic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MC P-1) were significantly increased by cyclic stretch. Northern blot ana lysis indicated that the mRNA levels of IL-8 and MCAF/MCP-1 were upreg ulated by cyclic stretch as a function of its intensity. Cytochalasin D, which disrupts the actin cytoskeleton, abolished the stretch-induce d gene expression of IL-8 and MCAF/MCP-1. In contrast, neither inhibit ion of stretch-activated ion channels nor disruption of microtubules a ffected the induction of these chemokines by cyclic stretch. Northern blot analysis using enzyme inhibitors showed that phospholipase C, pro tein kinase C, and tyrosine kinase were involved in the stretch-induce d gene expression of IL-8 and MCAF/MCP-1, whereas cAMP- or cGMP-depend ent protein kinase was not. In conclusion, cyclic stretch enhanced the secretion and gene expression of IL-8 and MCAF/MCP-1 in a stretch-dep endent fashion, and the integrity of the actin cytoskeleton and activi ties of phospholipase C, protein kinase C, and tyrosine kinase may be essential in the process of stretch-induced gene induction of IL-8 and MCAF/MCP-1.