1887

Abstract

Apoptosis induction of host macrophages has emerged as a common virulence mechanism among bacterial pathogens. Infection with is a leading cause of gastroenteritis worldwide and is characterized by an acute inflammatory response in the small intestine. The authors used the human monocytic cell line THP-1 to examine apoptosis induction and pro-inflammatory cytokine production during infection. Flow cytometric analysis revealed that 48 h after inoculation, a wild-type isolate induced apoptosis in 63 % of THP-1 cells while only 34 % of cells inoculated with a mutant, which does not secrete the Cia ( invasion antigens) proteins, underwent apoptosis. Complementation of the mutant resulted in levels of apoptosis similar to those induced by the wild-type isolate, suggesting that the Cia proteins have a role in apoptosis induction. It was shown that a proteinase K- and heat-stable component of also stimulated THP-1 apoptosis. Inoculation with a mutant indicated that lipooligosaccharide was not the stimulatory molecule. Immunoblot and ELISA analyses revealed that infection stimulated the synthesis, processing and secretion of interleukin 1 (IL-1). Inhibition of caspase 1 activity eliminated IL-1 processing and secretion, but did not affect apoptosis induction. In addition, treatment of cells with a caspase-9-specific inhibitor did not affect apoptosis induction, arguing against activation of an apoptotic pathway dependent on either caspase 1 or 9 activation. Collectively, these data suggest that the inoculation of macrophages with results in the processing of IL-1 and apoptosis through different regulatory pathways. Furthermore, these data argue that may use a mechanism distinct from and to initiate macrophage apoptosis and release of IL-1.

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2004-03-01
2024-05-12
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