TOLL-LIKE RECEPTOR 4 EXPRESSION ON CIRCULATING LEUCOCYTES IN HEMOLYTIC UREMIC SYNDROME

PATRICIA G. VALLES; SILVIA MELECHUK; ADRIANA GONZALEZ; WALTER MANUCHA; VICTORIA BOCANEGRA; ROBERTO VALLES

PEDIATRIC NEPHROLOGY

SPRINGER

Año: 2012 vol. 27 p. 407 - 415

0931-041X

Lipopolysaccharide stimulation of toll-like receptor 4 (TLR4) results in activation of signal transduction pathways leading to proinflammatory cytokine secretion. We investigated TLR4 surface receptor expression on peripheral blood neutrophils and monocytes and their ability to modulate the inflammatory cytokines release in fifteen patients 1,3 and 10 days after HUS onset. Seven EHEC-associated diarrhea patients and seven healthy controls were also studied. Isolated leucocytes from HUS onset patients exhibited significantly higher mRNA TLR4 expression than controls.Moreover TLR4 protein expression on neutrophils, determined by flow cytometry was found to be upregulated, driving dependent increased proinflammatory cytokines TNF-?¿, and IL-8 and decreased anti-inflammatory IL10 release in HUS onset compared to EHEC diarrhea and control children. Expression of TLR4 on neutrophils was positively correlated to serum TNF-?¿ levels. Conversely, significant reduction on neutrophils?LTLR4 receptor expression and lack of cytokine responsive elements activation was shown in patients 3 and 10 days after HUS onset. No differences were demonstrated in TLR4 receptor expression on monocytes among the studied groups. In summary, for our results TLR4 expression may be differently regulated on neutrophils and monocytes.They could dynamically be modulated across the early development of HUS on neutrophils, resulting in a negative regulation preceded by an overactivation of TLR4