Perturbation of actin dynamics induces NF-kappa B activation in myelomonocytic cells through an NADPH oxidase-dependent pathway

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-kappa B activation in myelomonocytic cells. The transduction pathway involved the I kappa B (inhibitory kappa B) kinase complex and a degradation of I kappa B alpha. We have shown that NF-kappa B activation in response to the perturbation of actin dynamics required reactive oxygen species. as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O-2(-) release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47(phox). NF-kappa B activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization.