CX3CL1 (fractalkine) and TNFα production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: the importance of CX3CR1 signaling

Szukiewicz, Dariusz; Kochanowski, Jan; Mittal, Tarun; Pyźlak, Michał; Szewczyk, Grzegorz; Cendrowski, Krzysztof

doi:10.1007/s00011-013-0687-z

Cited by 20 publications

(18 citation statements)

References 43 publications

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“…CX3CL1 is important in the recruitment of inflammatory cells into the vascular wall in endothelial cell injury (12,13). Previous studies have reported that TNF-α stimulates the CX3CL1/CX3CR1 inflammatory signaling pathway, whereas our previous studies revealed that the expression levels of TNF-α, CX3CL1 and CX3CR1 were significantly increased in rats with pulmonary embolism (3,14). Certain studies have reported that the presence and the stimulation of the CX3CL1 receptor, CX3CR1, is correlated with the reduced release of IL-1β and TNF-α (15,16).…”

Section: Discussioncontrasting

confidence: 62%

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Wang

Ying²,

Jiang

et al. 2018

Int J Mol Med

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The purpose of the present study was to examine whether aspirin interferes with the inflammatory response in a thrombus-stimulated lung microvascular endothelial cell (LMVEC) model. The LMVECs were randomly divided into eight groups: Normal group (group N), model group (group M), model + ASP group (group M+A), model+CX3CL1-short hairpin (sh)RNA group (group M+SH), model + CX3CL1-overexpression vector group (group M+CX3), model + ASP + shRNA group (group M+A+SH), model + ASP + CX3CL1-overexpression vector group (group M+A+CX3), and normal + virus control group (group N+V). The endothelial cells were cultured, and a thrombus was added to the cells. Briefly, 12 h following the precipitation of the thrombus, data from ELISA, reverse transcription-quantitative polymerase chain reaction analysis and confocal microscopy revealed that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, CX3C chemokine ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and nuclear factor-κB (NF-κB) in group M were increased, compared with those in group N (P<0.01). These levels, with the exception of TNF-α, were significantly lower in group M+SH, compared with those in group M (P<0.01). Furthermore, the levels of IL-6 in groups M+A, M+CX3 and M+A+CX3 were decreased, compared with those in group M (P<0.01); the level of TNF-α in group M+A+SH was decreased, compared with that in group M (P<0.01); the level of CX3CR1 waslower in groups M+A and M+A+SH, compared with that in group M (P<0.01), and the level of NF-κB in group M+SH was decreased, compared with the level in group M and group M+A (P<0.05). In conclusion, the thrombus-stimulated LMVEC model exhibited induced production of TNF-α, IL-6, CX3CL, CX3CR1, NF-κB and intercellular adhesion molecule-1. Furthermore, it was confirmed that the signaling pathways involving CX3CL1-NF-κB, IL-6 and TNF-α were partly inhibited by aspirin.

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Section: Discussioncontrasting

confidence: 62%

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Wang

Ying²,

Jiang

et al. 2018

Int J Mol Med

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“…The activation of signaling pathways involved in CX3CL1/CX3CR1 regulation in response to oxygen deprivation (e.g., pro-angiogenic) or related to cancerous mutations have been studied by many researchers. Changes in the cytokine network including TNF-α and CX3CL1 production and their respective receptor expression were striking [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways

Szukiewicz

Wojciechowska

Bilska

et al. 2015

Cardiovasc Drugs Ther

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PurposeTNF-α induces fractalkine (CX3CL1) and its receptor CX3CR1 in endothelial cells through NF-қB activation. NF-қB inhibitors may reduce the expression of CX3CL1, and modulation of the CX3CL1/CX3CR1 signaling was proposed as a new target for aspirin. We examined the effects of aspirin on CX3CL1 and TNF-α production, as well as CX3CR1 and TNFR1 expression.MethodsHUVECs isolated after term pregnancies (N = 28) were cultured in vitro. Lipopolysaccharide (1 μg/ml) was used as CX3CL1 inducer. HUVECs were exposed to six different concentrations of aspirin (between 1.0 and 6.0 mM) during 7 days. The levels of CX3CL1 and TNF-α in the culture media were measured using ELISA. After termination of the cultures, mean expressions of CX3CR1 and TNFR1 were examined in the immunostained paraffin sections using quantitative immunohistochemistry.ResultsAspirin significantly (p < 0.05) decreased CX3CL1 production, and the mean decrease in CX3CL1 production was inversely proportional to increased (p < 0.05) expression of CX3CR1. The combined mean CX3CL1 concentrations, including all time points, equaled 782.18 ± 74.4 pg/ml in aspirin treated HUVECs compared to a total concentration of 2467.53 ± 127.5 pg/ml combined from the respective time points in the controls.An inhibition of TNF-α production in HUVECs after pretreatment with aspirin was observed. Unlike in the case of CX3CR1 expression, there were no signs of TNFR1 upregulation.ConclusionsAutoregulation between CX3CL1 and CX3CR1 may explain overexpression of CX3CR1 as the compensatory effect in aspirin-treated HUVECs. Inhibition of CX3CR1 could prevent thrombotic complications in the early period after discontinuation of aspirin.

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“…As we known, CX3CL1 is one of the pivotal chemokines involved in T cell migration17. In the serum and synovial homogenate of CIA rats, we detected much higher concentrations of CX3CL1 than that in normal rats (Fig.…”

Section: Resultsmentioning

confidence: 57%

“…5C). The level of CX3CL1 is reported to be induced by TNF-α and other pro-inflammatory cytokines17. Both paroxetine and MTX could reduce the level of CX3CL1 in serum and synovial tissues but with different extent.…”

Section: Resultsmentioning

confidence: 99%

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

Wang

et al. 2017

Sci Rep

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T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4+ helper T (Th) cell and CD8+ cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX). In addition, both serum and synovial IL-1β, TNF-α and CX3CL1 expression was effectively inhibited in treated rats. In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. This study elucidates that paroxetine attenuates the symptoms of CIA rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway.

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CX3CL1 (fractalkine) and TNFα production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: the importance of CX3CR1 signaling

Cited by 20 publications

References 43 publications

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

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