Comparative evaluation of apoptosis induced by Shiga toxin 1 and/or lipopolysaccharides in human monocytic and macrophage-like cells.

The enteric pathogens Shigella dysenteriae serotype 1 and Shiga toxin-producing Escherichia coli share the property of expressing the structurally and functionally related cytotoxins that comprise the Shiga toxin (Stx) family. Stx-producing bacteria are causative agents of bloody diarrheal diseases that may progress to life threatening complications involving the destruction of blood vessels in the kidneys and the central nervous system (CNS). The precise mechanisms of toxin transport across the gut epithelial barrier, and the role of innate immunity in the development of systemic complications, remain to be fully characterized.

Chemokine expression in the monocytic cell line THP-1 in response to purified shiga toxin 1 and/or lipopolysaccharides.

Infections with Shiga toxin (Stx)-producing bacteria are associated with bloody diarrhea and postdiarrheal sequelae, including hemolytic uremic syndrome and central nervous system (CNS) abnormalities. Stx-induced intestinal, renal, and CNS vascular lesions may involve a localized production of proinflammatory cytokines in target organs, as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) up-regulate Stx receptor globotriaosylceramide (Gb(3)) expression on vascular endothelial cells. However, leukocyte recruitment to injured sites may also exacerbate vascular damage.

Regulation of proinflammatory cytokine expression by Shiga toxin 1 and/or lipopolysaccharides in the human monocytic cell line THP-1.

Infection with Shiga toxin (Stx)-producing bacteria and the subsequent release of Stxs and endotoxins into the bloodstream may damage blood vessels in the colon, kidneys, and central nervous system, leading to bloody diarrhea, acute renal failure, and neurological complications. The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) may contribute to the pathogenesis of Stx-induced vascular lesions by up-regulating toxin receptor expression on endothelial cells. We previously showed that macrophages treated with purified Shiga toxin 1 (Stx1) or lipopolysaccharides (LPS) secrete TNF-alpha and IL-1beta.