Abstract :
[en] Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion
and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear
factor kB (NF-kB) activation and expression of pro-inflammatory genes. In the present study,
we demonstrated that reorganization of actin cytoskeleton induced by Cytochalasin D
(CytD), an actin-polymerization inhibitor, enhanced il-8 gene expression induced by TNFa
and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional
mechanisms were involved. CytD potentiated NF-kB-mediated transcription induced by
both TNFa and LPS but via different mechanisms. In the case of LPS, the perturbation of actin
dynamics increased the TLR4 levels at the cell membrane and consequently enhanced the
IKK complex activation and NF-kB nuclear translocation. However, the canonical pathway
involving the IKK complex and leading to the NF-kB translocation into the nucleus was not
affected by actin remodelling in the case of TNFa. Interestingly, actin disruption primed p65
phosphorylation induced by TNFa and LPS, on Ser276 and Ser536, respectively, which
suggested actin cytoskeleton could also modulate p65 transactivating activity.
Name of the research project :
Modulation of the NF-KappaB activation pathways by the actin cytoskeleton
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