17Beta-estradiol inhibits the adhesion of leukocytes in TNF-alpha stimulated human endothelial cells by blocking IL-8 and MCP-1 secretion, but not its transcription.
Inflammation, and especially mononuclear cell adhesion to endothelium, is an important physiopathological component of atherosclerosis. Since coronary heart disease in women of reproductive age and/or with estrogen replacement therapy is reduced, our aim was to determine if 17beta-estradiol had a regulatory effect on the adhesion of lymphocytes to the endothelium. We performed U-937 cells adhesion assays in TNF-alpha-stimulated HUVECs, and we also quantitated IL-8 and MCP-1 in culture supernatants, in the presence or not of 17beta-estradiol. The presence of alpha- and beta-estrogen receptors was determined by Western blot and RT-PCR, respectively, whereas the transcription of both chemokines was evaluated by RT-PCR. The results showed a 35% decrease in the adhesion of U-937 monocyte cells to TNF-alpha-stimulated HUVECs, and a 54% and 65% inhibition of TNF-alpha-induced IL-8 and MCP-1 secretion by physiological and physiologically high doses of 17beta-estradiol. The hormone did not affect the transcription of both chemokine genes. Tamoxifen reverted the inhibitory effect induced by 17beta-estradiol. In conclusion, 17beta-estradiol modifies the adhesion of leukocytes to endothelial cells by inhibiting the secretion, but not the gene transcription, of proinflammatory chemokines.
Depto. Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Tlalpan 14080, D.F., México, Mexico.
Emma
E
Rodríguez
Rebeca
R
López
Araceli
A
Paez
Felipe
F
Massó
Luis F
LF
Montaño
D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D018932:Chemokine CCL2; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D012313:RNA