Perturbation of actin dynamics induces NF-kappaB activation in myelomonocytic cells through an NADPH oxidase-dependent pathway.
Although several reports showed the effect of compounds disrupting microtubules on NF-kappaB (nuclear factor kappaB) 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-kappaB activation in myelomonocytic cells. The transduction pathway involved the IkappaB (inhibitory kappaB) kinase complex and a degradation of IkappaBalpha. We have shown that NF-kappaB 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 O2- release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47phox. NF-kappaB 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.
Kustermans
Gaelle
G
Laboratory of Virology and Immunology, Institute of Pathology, University of Liège, B-4000 Liege, Belgium.
El Benna
Jamel
J
Piette
Jacques
J
Legrand-Poels
Sylvie
S
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D047630:Depsipeptides / Q000494:pharmacology; D006801:Humans; D051550:I-kappa B Kinase; D009000:Monocytes / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
D000199:Actins; D047630:Depsipeptides; D016328:NF-kappa B; C057531:jasplakinolide; D015638:Cytochalasin D; D019255:NADPH Oxidases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D010100:Oxygen