Actin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells

Kustermans, Gaelle; Mjiyad, Nadia El; Horion, Julie; Jacobs, Nathalie; Piette, Jacques; Legrand-Poels, Sylvie

doi:10.1016/j.bcp.2008.08.017

Cited by 33 publications

(32 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was further confirmed by the western blotting results. Cyt D and Jas were used, respectively, to destabilize or stabilize actin filaments [8]. Analysis of nuclear extracts by western blotting analysis showed that ADMA (100 mM) increased the nuclear RelA/ P65 level ( Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

Wei

Zhang

Wang

et al. 2013

ABBS

View full text Add to dashboard Cite

Asymmetric dimethylarginine (ADMA) activates nuclear factor (NF)-kB in endothelial cells, while actin-stabilizing or -destabilizing drugs prevent ADMA-induced activation of NF-kB. Here we investigated how actin-targeting drugs regulated ADMA-induced NF-kB activation in endothelial cells. Human umbilical vein endothelial cells were treated with ADMA for 24 h in the absence and presence of cytochalasin D or jasplakinolide. Expression levels of proteins and genes were measured by immunoblotting and reversetranscription polymerase chain reaction, respectively. Chromatin immunoprecipitation was used to detect the binding of NF-kB to the vascular cell adhesion molecule 1 (VCAM-1) promoter. The association of actin with RelA/ P65 was detected by immunoprecipitation. It was demonstrated that ADMA induced IkBa degradation, increased nuclear RelA/P65 translocation, and promoted the binding of NF-kB to the VCAM-1 promoter. Consequently, this increased the expression of VCAM-1. In parallel studies, actin-stabilizing and -destabilizing drugs decreased ADMAinduced RelA/P65 nuclear translocation, interfered with NF-kB binding to the VCAM-1 promoter and prevented the expression of VCAM-1. This was independent of total RelA/ P65 levels and ADMA-induced IkBa degradation. Most importantly, the association of RelA/P65 with actin was increased after stimulation with ADMA, and impaired after treatment with actin-targeting drugs. In brief, actinstabilizing or -destabilizing drugs interfere with the ADMAinduced association of RelA/P65 with actin, and consequently disrupt NF-kB activation.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Several studies have suggested that a variety of agents that stabilize or destabilize the actin cytoskeleton are capable of inhibiting NF-kB [8,9]. Actin filaments can be either stable, with their lengths precisely specified, or dynamic, undergoing rapid polymer elongation and shrinkage.…”

Section: Introductionmentioning

confidence: 99%

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

Wei

Zhang

Wang

et al. 2013

ABBS

View full text Add to dashboard Cite

show abstract

“…As shown in Figure, signaling via NF-kB [8] and Nrf2 [9] can both depend on cytoskeletal changes, indicating that SP-A-mediated modulation of the actin cytoskeleton could have significant effects on AM responses. Moreover, the SP-A -/-rescue experiment [1] points to the possibility and feasibility of using SP-A as a therapeutic intervention in lung diseases influenced by innate immunity.…”

mentioning

confidence: 94%

“…The actin cytoskeleton is highly regulated and dynamic, with globular (G) and filamentous (F) actin, under the influence of many actin binding proteins, constantly changing by polymerization, depolymerization, branching, and remodeling, modulating inflammatory response and oxidative stress ( Figure 1). Figure, signaling via NF-kB [8] and Nrf2 [9] can both depend on cytoskeletal changes, indicating that SP-A-mediated modulation of the actin cytoskeleton could have significant effects on AM responses. Moreover, the SP-A -/-rescue experiment [1] points to the possibility and feasibility of using SP-A as a therapeutic intervention in lung diseases influenced by innate immunity.…”

mentioning

confidence: 97%

“…[1] show that SP-A has significant impact on the AM expression profile and specifically on the cytoskeletal/actin-related proteins. Based on the literature cytoskeletal changes may affect several signaling processes including NF-kB [8] and Nrf2 [9]. These processes in turn via transcriptional regulation modulate the inflammatory response and the response to oxidative stress.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Human Surfactant Proteins (SP-) A1 and SP-A2: to Include or Not in Surfactant Replacement Therapy, and If Yes, Both or Which One?

Floros

Phelps²

2014

J Neonatal Biol

View full text Add to dashboard Cite

Based on a large number of animal studies, surfactant protein A plays important roles in lung innate immunity under basal conditions and in response to various insults such as infection and oxidative stress. SP-A interacts with the Alveolar Macrophage (AM), the sentinel cell of innate immunity, and regulates many of its functions. These include the ability of the AM to produce cytokines and to carry out phagocytosis of various pathogens. Moreover, the AM proteomic expression profile has been shown to be significantly affected by SP-A. In a study where SP-A -/-mice were treated (or rescued) in vivo with a single dose of human SP-A, the treatment nearly restored the AM proteomic expression to that of the wild type [1], supporting a role of SP-A on AM protein expression. Among the protein groups affected were actin-related/cytoskeletal proteins, which was the major group, proteins regulating inflammatory processes, and proteins related to Nrf2-mediated oxidative stress. Of interest, earlier studies have also indicated a role for SP-A in actin filament dynamics via its ability to enhance cell migration and AM chemotaxis [2], phagocytosis [3], other actin-dependent processes [4][5][6] and F-actin assembly [7]. The actin cytoskeleton is highly regulated and dynamic, with globular (G) and filamentous (F) actin, under the influence of many actin binding proteins, constantly changing by polymerization, depolymerization, branching, and remodeling, modulating inflammatory response and oxidative stress ( Figure 1). Figure, signaling via NF-kB [8] and Nrf2 [9] can both depend on cytoskeletal changes, indicating that SP-A-mediated modulation of the actin cytoskeleton could have significant effects on AM responses. Moreover, the SP-A -/-rescue experiment [1] points to the possibility and feasibility of using SP-A as a therapeutic intervention in lung diseases influenced by innate immunity. Furthermore, based on animal studies [10] where small amounts of SP-A elicited significant differences in the AM proteome, it is possible that the SP-A amount needed may not be high, although, further experimentation will be needed to determine optimal amount and efficacy in the clinical setting. As shown inHowever, humans, (unlike rodents) have two genes, SFTPA1 (SP-A1) and SFTPA2 (SP-A2) with several genetic variants identified for each SP-A1 and SP-A2 gene. These variants have been associated with many lung diseases including neonatal diseases, such as Respiratory Distress Syndrome (RDS) and Bronchopulmonary Dysplasia (BPD) [11]. The SP-A1 and SP-A2 gene products have been shown to differ in several functions related to innate immunity [12] and in surfactantrelated functions [13,14]. These differences have been reviewed previously [12] and include differences in their oligomerization status [13,15,16], their ability to form phospholipid monolayers [17], their ability to bind sugars [18], and their ability to enhance the phagocytic activity and cytokine production by the alveolar macrophages and macrophage-like cell lines, respectively [3,...

show abstract

Functional compartmentalisation of NF‐κB‐associated proteins in A431 cells

Bolshakova

Magnusson

Пинаев

et al. 2013

Cell Biology International

View full text Add to dashboard Cite

NF-kB proteins belong to a family of ubiquitous transcription factors involved in a number of cellular responses. While the pathways of NF-kB activation and input into the regulation of gene activity have been comprehensively investigated, its cytoplasmic functions are poorly understood. In this study we addressed effects of the compartmentalisation of NF-kB proteins RelA/p65 and p50 in relation to the inhibitor IkB-a, using fibronectin (FN) and epidermal growth factor (EGF) for environmental stimulation of epidermoid carcinoma A431 cells. We thus assessed the presence of NF-kB family proteins in the cytosol, membrane, nuclear and cytoskeletal fractions with a special attention to the cytoskeletal fraction to define whether NFkB was active or not. Sub-cellular fractionation demonstrated that the proportion of RelA/p65 differed in diverse sub-cellular fractions, and that the cytoskeleton harboured about 7% thereof. Neither the nuclear nor the cytoskeleton fraction did contain IkB-a. The cytoskeleton binding of RelA/p65 and p50 was further confirmed by co-localisation and electron microscopy data. During 30-min EGF stimulation similar dynamics were found for RelA/p65 and IkB-a in the cytosol, RelA/p65 and p50 in the nucleus and p50 and IkB-a in the membrane. Furthermore, EGF stimulation for 30 min resulted in a threefold accumulation of RelA/p65 in cytoskeletal fraction. Our results suggest that nuclear-, membrane- and cytoskeleton-associated NF-kB are dynamic and comprise active pools, whereas the cytoplasmic is more constant and likely non-active due to the presence of IkB-a. Moreover, we discovered the existence of a dynamic, IkB-a-free pool of RelA/p65 associated with cytoskeletal fraction, what argues for a special regulatory role of the cytoskeleton in NF-kB stimulation.

show abstract

Actin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells

Cited by 33 publications

References 78 publications

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

Human Surfactant Proteins (SP-) A1 and SP-A2: to Include or Not in Surfactant Replacement Therapy, and If Yes, Both or Which One?

Functional compartmentalisation of NF‐κB‐associated proteins in A431 cells

Contact Info

Product

Resources

About