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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

Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico

J Guevara

Depto. Bioquímica, Facultad de Medicina, UNAM, Mexico

A Paez

Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico

E Zapata

Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico

MT Collados

Depto. Biotecnología, Tecnologico de Monterrey, Nuevo León, Mexico

TI Fortoul

Depto. Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico

R Lopez-Marure

Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico

F Masso

Depto. Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico

LF Montaño

Depto. Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico

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- and/or physiological and pharmacological doses of 17-β 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- 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- treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF--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--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.

Key Words: adhesion molecules • endothelial cells • estradiol • inflammation • lupus

Lupus, Vol. 17, No. 12, 1086-1095 (2008)
DOI: 10.1177/0961203308093827


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