Toll-like receptor 4 expression on circulating leucocytes in hemolytic uremic syndrome |
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Authors: | Patricia G Vallés Silvia Melechuck Adriana González Walter Manucha Victoria Bocanegra Roberto Vallés |
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Institution: | 1.área de Fisiología Patológica Departamento de Patología Facultad de Ciencias Médicas,Universidad Nacional de Cuyo, Centro Universitario,Mendoza,Argentina;2.Servicio de Nefrología Departamento de Pediatría,Hospital Humberto Notti,Mendoza,Argentina;3.Instituto de Inmunología Hospital Central Facultad de Ciencias Médicas,Universidad Nacional de Cuyo,Mendoza,Argentina;4.IMBECU-CONICET (National Council of Scientific and Technical Research of Argentina),Mendoza,Argentina |
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Abstract: | 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 on neutrophils was positively correlated with serum TNF-α 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. |
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