Artículo
Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
Landoni, Verónica Inés
; de Campos Nebel, Ildefonso Marcelo
; Schierloh, Luis Pablo
; Calatayud, Cecilia Alicia
; Fernández, Gabriela Cristina
; Ramos, Maria Victoria
; Rearte, María Bárbara
; Palermo, Marina Sandra
; Isturiz, Martín Amadeo
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Fecha de publicación:
03/2010
Editorial:
American Society for Microbiology
Revista:
Infection and Immunity
ISSN:
0019-9567
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Palabras clave:
Astrocytes
,
Shiga Toxin 1
,
Hemolytic-Uremic Syndrome
,
Brain Inflammation
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Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Landoni, Verónica Inés; de Campos Nebel, Ildefonso Marcelo; Schierloh, Luis Pablo; Calatayud, Cecilia Alicia; Fernández, Gabriela Cristina; et al.; Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha; American Society for Microbiology; Infection and Immunity; 78; 3; 3-2010; 1193-1201
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