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Stress oxydatif, inflammation vasculaire et métalloprotéinases : étude in vitro sur un modèle de coculture

Abstract : During atherosclerosis leucocytes invade the vascular wall, inducing inflammation and production of oxidative stress by reactive oxygen species (ROS). We tested the effects of an oxidative stress and/or potential interactions between a neutrophil model ( [different from]HL60) and human coronary endothelial (HCAEC) or smooth muscle (HCSMC) cells, on [different from]HL60 mobility and production and activity of cellular metalloproteinases. Cell passaging of the promyelocytic HL60 cell line, differentiated by DMSO in a neutrophil model ([different from]HL60), induces variations in cell mobility and production of MMP9. ROS from biochemical or cellular sources did not modify MMP2 or MMP9 activity in HCAEC or HCSMC. There is no modification of MMPs activities in [different from]HL60/HCAEC cocultures, but stimulation of ?HL60 MMP9 activity in [different from]HL60/HCSMC cocultures. Basal migration capacities and N-formyl-L-Methionyl-LLeucyl-L-Phenylalanine -stimulated invasion abilities of [different from]HL60 increase in presence of HCSMC. Antioxidant enzymes barely change [different from]HL60 mobility, increase expression and production of [different from]HL60 MMP9 and seem to reduce the stimulating effect of HCSMC on [different from]HL60 MMP9 production. HCSMC also express and/or secrete somecytokines (IL8, IL6, IL1[bêta], CCL2, CXCL12) implicated in atherosclerosis. In conclusion, interactions between [different from]HL60 and HCSMC induce an increase in MMP9 secretion, which is modulated by ROS, and a stimulation of [different from]HL60 mobility. Expression by HCSMC of inflammatory cytokines implicated in atherosclerosis allows to identify potential candidates responsible for the secretory and/or migratory response of [different from]HL60.
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Yohann Bernard. Stress oxydatif, inflammation vasculaire et métalloprotéinases : étude in vitro sur un modèle de coculture. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10067⟩. ⟨tel-01777279⟩



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