Toll-like receptor 4 expression on circulating leucocytes 5 in hemolytic uremic syndrome

GARRAMUÑO DE VALLES PATRICIA; MELECHUK SILVIA; GONZALEZ ADRIANA; MANUCHA WALTER; BOCANEGRA VICTORIA; VALLÉS ROBERTO

PEDIATRIC NEPHROLOGY

SPRINGER

Año: 2011 p. 407 - 415

0931-041X

Lipopolysaccharide stimulation of toll-like receptor 4 (TLR4) activates 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  inflammatory cytokine release in 15 patients 1, 3, and 10 days after hemolytic uremic syndrome (HUS) onset. Seven patients with Escherichia coli (EHEC)-associated diarrhea and seven healthy controls were also studied. Isolated leucocytes from HUS-onset patients exhibited significantly higher messenger RNA (mRNA) TLR4 expression than controls. Moreover, TLR4 protein expression on neutrophils, determined by flow cytometry, was upregulated, driving dependent proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) increase, and decreased anti-inflammatory IL-10 release at HUS onset compared with patients with EHEC diarrhea and controls. TLR4 expression 28 on neutrophils was positively correlated with serum TNF-α 29 levels. Conversely, significant reduction of neutrophil TLR4 receptor expression and lack of cytokine-responsive element 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. Our  results suggest TLR4 expression may be differently regulated on neutrophils and monocytes. They could be dynamically  modulated across the early development of HUS on neutrophils, resulting in negative regulation preceded by TLR4 overactivation.