Abstract
Shiga toxins are a family of genetically and structurally related
toxins that are the primary virulence factors produced
by the bacterial pathogens Shigella dysenteriae serotype 1
and certain Escherichia coli strains. The toxins are multifunctional
proteins inducing protein biosynthesis inhibition,
ribotoxic and ER stress responses, apoptosis, autophagy, and
inflammatory cytokine and chemokine production. The regulated
induction of inflammatory responses is key to minimizing
damage upon injury or pathogen-mediated infections,
requiring the concerted activation of multiple signaling pathways
to control cytokine/chemokine expression. Activation
of host cell signaling cascades is essential for Shiga toxinmediated
proinflammatory responses and the contribution
of the toxins to virulence. Many studies have been reported
defining the inflammatory response to Shiga toxins in vivo
and in vitro, including production and secretion of tumor
necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), macrophage
inflammatory protein-1α/β (MIP-1α/β), macrophage
chemoattractant monocyte chemoattractant protein
1 (MCP-1), interleukin 8 (IL-8), interleukin 6 (IL-6), and
Groβ. These cytokines and chemokines may contribute to
damage in the colon and development of life threatening
conditions such as acute renal failure (hemolytic uremic
syndrome) and neurological abnormalities. In this review,
we summarize recent findings in Shiga toxin-mediated inflammatory
responses by different types of cells in vitro and
in animal models. Signaling pathways involved in the inflammatory
responses are briefly reviewed.
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