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

GARRAMUÑO VALLÉS , PATRICIA; MELECHUCK SILVIA; GONZÁLEZ ADRIANA; MANUCHA WALTER; BOCANEGRA VICTORIA; VALLÉS ROBERTO

PEDIATRIC NEPHROLOGY

SPRINGER

Lugar: Berlin; Año: 2012 vol. 27 p. 407 - 415

0931-041X

Abstract Lipopolysaccharide stimulation of toll-likereceptor 4 (TLR4) activates signal transduction pathwaysleading to proinflammatory cytokine secretion. We investigatedTLR4 surface receptor expression on peripheral bloodneutrophils and monocytes and their ability to modulateinflammatory cytokine release in 15 patients 1, 3, and 10 daysafter hemolytic uremic syndrome (HUS) onset. Seven patientswith Escherichia coli (EHEC)-associated diarrhea and sevenhealthy controls were also studied. Isolated leucocytes fromHUS-onset patients exhibited significantly higher messengerRNA (mRNA) TLR4 expression than controls. Moreover,TLR4 protein expression on neutrophils, determined byflow cytometry, was upregulated, driving dependentproinflammatory cytokine, tumor necrosis factor alpha(TNF-α), and interleukin 8 (IL-8) increase, and decreasedanti-inflammatory IL-10 release at HUS onset compared withpatients with EHEC diarrhea and controls. TLR4 expressionon neutrophils was positively correlated with serum TNF-αlevels. Conversely, significant reduction of neutrophil TLR4receptor expression and lack of cytokine-responsive elementactivation was shown in patients 3 and 10 days after HUSonset. No differences were demonstrated in TLR4 receptorexpression on monocytes among the studied groups. Ourresults suggest TLR4 expression may be differently regulatedon neutrophils and monocytes. They could be dynamicallymodulated across the early development of HUS on neutrophils,resulting in negative regulation preceded by TLR4overactivation.