title: Racial differences in tumor necrosis factor-α-induced endothelial microparticles and interleukin-6 production.
abstract: African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF-α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/μg in the AA and 30.9 ± 14.9 pg/mL/μg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α.
authors.affiliation: Hypertension, Molecular and Applied Physiology Laboratory, School of Medicine, Temple University, Philadelphia, PA 19122, USA. brownmd@temple.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brown
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Feairheller
authors.forename: Sunny
authors.initials: S
authors.lastname: Thakkar
authors.forename: Praveen
authors.initials: P
authors.lastname: Veerabhadrappa
authors.forename: Joon-Young
authors.initials: JY
authors.lastname: Park
mesh_terms: D001741:Black or African American; D015153:Blotting, Western; D048430:Cell Shape; D055252:Cell-Derived Microparticles / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D015143:Philadelphia / Q000453:epidemiology; D011994:Recombinant Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D044465:White People
chemical_list: C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase