Actin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells
Actin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells
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DOI：
10.1016/j.bcp.2008.08.017
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发表时间：
2008-11-15
影响因子：
5.8
通讯作者：
Legrand-Poels, Sylvie
中科院分区：
文献类型：
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作者：
Kustermans, Gaelle;El Mjiyad, Nadia;Legrand-Poels, Sylvie
许多生理病理事件，如吞噬、病原体侵袭、细胞粘附和黑钙化等，都伴随着核因子κ B （nf - κ B）的激活和促炎基因的表达。在本研究中，我们证实了肌动蛋白聚合抑制剂Cytochalasin D （CytD）诱导的肌动蛋白细胞骨架重组，增强了TNF α和LPS诱导的HL-60单核细胞样细胞中il-8基因的表达。转录和转录后机制都参与其中。CytD增强tnf fa和LPS诱导的NF-kappa b介导的转录，但通过不同的机制。在LPS的情况下，肌动蛋白动力学的扰动增加了细胞膜上的TLR4水平，从而增强了IKK复合物的激活和NF-kappa B核易位。然而，在TNF α的情况下，涉及IKK复合物并导致nf - κ B易位到细胞核的典型途径不受肌动蛋白重塑的影响。有趣的是，肌动蛋白破坏引发了TNFa和LPS诱导的p65磷酸化，分别在Ser（276）和Ser（536）上，这表明肌动蛋白细胞骨架也可以调节p65反激活活性。(C) 2008爱思唯尔公司版权所有。
Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chernotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kappa B (NF-kappa B) 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 TNF alpha and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional mechanisms were involved. CytD potentiated NF-kappa B-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-kappa B nuclear translocation. However, the canonical pathway involving the IKK complex and leading to the NF-kappa B translocation into the nucleus was not affected by actin remodelling in the case of TNF alpha. Interestingly, actin disruption primed p65 phosphorylation induced by TNFa and LPS, on Ser(276) and Ser(536), respectively, which suggested actin cytoskeleton could also modulate p65 transactivating activity. (C) 2008 Elsevier Inc. All rights reserved.