title: Actin cytoskeleton differentially modulates NF-kappaB-mediated IL-8 expression in myelomonocytic cells.
abstract: Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kappaB (NF-kappaB) 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 TNFalpha and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional mechanisms were involved. CytD potentiated NF-kappaB-mediated transcription induced by both TNFalpha 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-kappaB nuclear translocation. However, the canonical pathway involving the IKK complex and leading to the NF-kappaB translocation into the nucleus was not affected by actin remodelling in the case of TNFalpha. Interestingly, actin disruption primed p65 phosphorylation induced by TNFalpha and LPS, on Ser(276) and Ser(536), respectively, which suggested actin cytoskeleton could also modulate p65 transactivating activity.
authors.affiliation: Virology and Immunology Unit, GIGA-R, GIGA B34, University of Liège, 4000 Liège, Belgium.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Kustermans
authors.forename: Nadia
authors.initials: N
authors.lastname: El Mjiyad
authors.forename: Julie
authors.initials: J
authors.lastname: Horion
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jacobs
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Legrand-Poels
mesh_terms: D000199:Actins / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*
chemical_list: D000199:Actins; D016209:Interleukin-8; D016328:NF-kappa B