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.
Rodríguez
Emma
E
Depto. Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Tlalpan 14080, D.F., México, Mexico.
López
Rebeca
R
Paez
Araceli
A
Massó
Felipe
F
Montaño
Luis F
LF
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