Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in human umbilical vein endothelial cells.
Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis. We determined the effect of pharmacological doses of DHEA upon the adhesion of monocytic U937 cells to human umbilical vein endothelial cells (HUVEC), as well as the expression of adhesion and chemoattractant molecules, the translocation of NF-kappaB, the degradation of IkappaB-alpha and the production of reactive oxygen species (ROS) in HUVEC. Adhesion of U937 cells to DHEA-treated HUVEC was evaluated by co-culture experiments using [(3)H]-thymidine-labeled U937 cells. The expression of adhesion and chemoattractant molecules was evaluated by flow cytometry and RT-PCR, respectively; NF-kappaB translocation was determined by Electrophoretic Mobility Shift Assay (EMSA) and IkappaB-alpha degradation by Western blot. ROS production was determined by the reduction of fluorescent DCFDA. TNF-alpha was used to induce inflammatory responses in HUVEC. One hundred micromolar of DHEA-treatment inhibited the TNF-alpha-induced expression of ICAM-1, E-selectin, ROS production and U937 cells adhesion to HUVEC, and interfered with NF-kappaB translocation and IkappaB-alpha degradation. DHEA at the above mention concentration also inhibited the mRNA expression of MCP-1 and IL-8 in basal conditions but not in TNF-alpha-stimulated conditions. Our results suggest that DHEA inhibits the expression of molecules involved in the inflammatory process, therefore it could be used as an alternative in the treatment of chronic inflammatory diseases such as atherosclerosis.
Departamento de Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano No. 1, Colonia Sección 16, Tlalpan, C.P. 14080, México D.F., Mexico.
Gisela
G
Gutiérrez
Criselda
C
Mendoza
Estrella
E
Zapata
Angélica
A
Montiel
Elba
E
Reyes
Luis Felipe
LF
Montaño
Rebeca
R
López-Marure
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control
D000276:Adjuvants, Immunologic; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D003687:Dehydroepiandrosterone