title: Shear stress attenuates tumor necrosis factor-alpha-induced monocyte chemotactic protein-1 expressions in endothelial cells.
abstract: The interplay between shear stress and cytokines in regulating vascular endothelial function remains largely unexplored. In the present study, the potential role of shear stress in regulating tumor necrosis factor-alpha (TNF-alpha)-induced gene expression in endothelial cells (ECs) was investigated. The TNF-alpha-induced monocyte chemotactic protein-1 (MCP-1) mRNA expressions were significantly attenuated in ECs subjected to a high level of shear stress (20 dynes/cm2) for 4 or 24 h prior to the addition of TNF-alpha in the presence of flow. Less inhibition of TNF-alpha-induced MCP-1 mRNA expression was found in ECs pre-exposed to a low level of shear stress (1.2 dynes/cm2) for 24 h as compared with the cells presheared (pre-exposed to shear stress) for 4 h. Simultaneous exposure of ECs to TNF-alpha and a high or low level of shear stress down-regulated TNF-alpha-induced MCP-1 gene expressions, suggesting that the post-flow condition modulates endothelial responses to cytokine stimulation. Individually or combined, an endothelial nitric oxide synthase (eNOS) inhibitor and a glutathione (GSH) biosynthesis inhibitor had no effect on this shear stress-mediated inhibition. Moreover, in ECs either presheared or remained in a static condition prior to stimulation by TNF-alpha while under shear flow, the ability of TNF-alpha to induce AP-1-DNA binding activity in the nucleus was reduced. Our findings suggest that shear stress plays a protective role in vascular homeostasis by inhibiting endothelial responses to cytokine stimulation.
authors.affiliation: Division of Medical Engineering Research, National Health Research Institutes, Taipei 114, Taiwan, ROC. jjchiu@nhri.org.tw
authors.forename: Jeng-Jiann
authors.initials: JJ
authors.lastname: Chiu
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Lee
authors.forename: Chih-I
authors.initials: CI
authors.lastname: Lee
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Chen
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Ko
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Lien
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione