ISSN:
1365-2958
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
,
Medicine
Notes:
Listeriolysin O (LLO) is a pore-forming cytolysin secreted by the pathogen Listeria monocytogenes and is required for its intracellular survival. We recently demonstrated that in endothelial cells, LLO activates the NF-κB signalling pathway. In this work, we studied the LLO-induced molecular cascade of NF-κB activation with a cellular model extensively used to analyse the signalling pathway of NF-κB activation, i.e. the human embryonic kidney HEK-293 cell line and its derivatives (transfectants or mutants). When the stably transfected derivative HEK-293 cells expressing IL-1RI were exposed to LLO, a strong NF-κB activation was detected, contrasting with other cell lines (HEK-293 wild type, HEK-293.T and COS) expressing a very low level of IL-1RI. Although a delayed kinetics of LLO-dependent NF-κB activation suggests an autocrine or paracrine IL-1-dependent pathway, we found that LLO-dependent NF-κB activation did not require the IL-1 protein synthesis nor the interaction with the IL-1RI specific receptor. Herein, we demonstrated that LLO-dependent NF-κB activation requires the activation of the IκB kinase β (IKKβ) subunit of IKK complex to phosphorylate and degrade cytoplasmic IκBα, a natural inhibitor of NF-κB. The activation induced by LLO does not require the adapters MyD88 and IL-1R-associated kinase (IRAK). We suggested that LLO induces a distinct signalling pathway from that of IL-1 and its receptor.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2958.2002.02973.x
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