title: The altered expression of inflammation-related molecules and secretion of IL-6 and IL-8 by HUVEC from newborns with maternal inactive systemic lupus erythematosus is modified by estrogens.
abstract: Systemic lupus erythematosus (SLE) predominantly affects women, especially those in reproductive age. Genetic contributions to disease susceptibility as well as immune dysregulation, particularly persistent inflammatory responses, are considered essential features. Our aim was to determine whether human umbilical vein endothelial cells (HUVEC) isolated from healthy newborns to women with inactive SLE show inflammation-related abnormalities that might lead to an early development of SLE in the offsprings. HUVEC isolated from six women with inactive SLE were stimulated with 2.5 ng/mL of TNF-alpha and/or physiological and pharmacological doses of 17-I(2) estradiol (E2). Then the expression of VCAM-1, ICAM-1, E-selectin, toll-like receptor-9 (TLR-9), heat shock protein 70 (HSP70) and HSP90 were measured. The concentrations of IL-6, IL-8, and IL-10 were also determined in maternal serum and in TNF-alpha stimulated and non-stimulated HUVEC culture supernatant. HUVEC from children with no family history of autoimmune disease served as controls. Our results showed that in HUVEC from SLE+ mothers, a constitutively low expression of adhesion molecules was enhanced by TNF-alpha treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF-alpha-treated cells. IL-6 was constitutively higher in SLE+ HUVEC, whereas IL-8 was lower; E2 treatment diminished the latter. The E2 had no effect upon IL-6 and IL-8 secretions in TNF-alpha-treated cells. SLE+ HUVEC showed a disordered cytoskeleton and overexpressed HSP70, HSP90, and TLR-9. Our results indicate that endothelial cells of newborns to SLE+ mothers are in a proinflammatory condition which can be upregulated by estrogens.
authors.affiliation: Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico. emarod2@yahoo.com.mx
authors.forename: E
authors.initials: E
authors.lastname: Rodriguez
authors.forename: J
authors.initials: J
authors.lastname: Guevara
authors.forename: A
authors.initials: A
authors.lastname: Paez
authors.forename: E
authors.initials: E
authors.lastname: Zapata
authors.forename: M T
authors.initials: MT
authors.lastname: Collados
authors.forename: T I
authors.initials: TI
authors.lastname: Fortoul
authors.forename: R
authors.initials: R
authors.lastname: Lopez-Marure
authors.forename: F
authors.initials: F
authors.lastname: Masso
authors.forename: L F
authors.initials: LF
authors.lastname: Montaño
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D055815:Young Adult
chemical_list: D019040:E-Selectin; D004967:Estrogens; D006360:Heat-Shock Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018799:Intercellular Adhesion Molecule-1