Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate

Dueñas, Antonio; Aceves, Mónica; Fernández‐Pisonero, Isabel; Gómez, Cristina; Orduña, Antonio; Crespo, Mariano Sánchez; García-Rodríguez, Carmen

doi:10.1093/cvr/cvn087

Cited by 47 publications

(47 citation statements)

References 46 publications

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“…Our results are in accordance with the cooperation of TLR4 and S1P receptors to enhance inflammatory cytokine production in human gingival epithelial cells (33). In contrast, in a previous study we have observed that TLR2 and S1P 1/2 receptors interaction resulted in the inhibition of chemokine production in human monocytes/ macrophages (20). These apparent discrepancies could be explained by the differences in the TLR expression in these cells, as TLR2 expression in endothelial cells is low.…”

Section: Discussionsupporting

confidence: 90%

“…First-strand cDNA was synthesized from total RNA by the reverse transcription reaction and later amplified by PCR. Primer sequences for human S1P receptors and TLRs were as described (20,21). cDNA was amplified in a PTC-200 apparatus equipped with a Chromo4 detector (BioRad) using SYBR Green I mix containing HotStart polymerase (ABgene).…”

Section: Real-time Rt-pcr Analysismentioning

confidence: 99%

“…Cells were stimulated with TLR ligands (0.1-5 mg/ml LPS or 100-300 ng/ ml Pam 3 CSK4) in or not in the presence of S1P (0.1-5 mM), and cell lysates were analyzed by Western blot as described earlier (20). Expression of proinflammatory molecules was detected with Abs against human COX-2 and ICAM-1.…”

Section: Immunodetection Of Icam-1 Cox-2 P-nf-kb and Mapksmentioning

confidence: 99%

“…Validated siRNA duplexes specific for S1P 1 and S1P 3 were as described (20). Quantitative PCR was performed to confirm downloading of human S1P receptors as described (20).…”

Section: Sirna Experimentsmentioning

confidence: 99%

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Lipopolysaccharide and Sphingosine-1-Phosphate Cooperate To Induce Inflammatory Molecules and Leukocyte Adhesion in Endothelial Cells

Fernández‐Pisonero

Dueñas

Barreiro

et al. 2012

The Journal of Immunology

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Given that TLRs and sphingosine-1-phosphate (S1P) are key players in inflammation, we explored the potential interplay between TLRs and S1P in the adhesion/inflammatory pathways in primary human endothelial cells. As determined by Western blot and flow cytometry, cells treated with LPS (a TLR4 ligand) and S1P showed significantly enhanced expression of adhesion molecules such as ICAM-1 and E-selectin compared with the effect of either ligand alone. Cell-type differences on E-selectin upregulation were observed. In contrast, no cooperation effect on ICAM-1 or E-selectin was observed with a TLR2/TLR1 ligand. Consistent with an increase in adhesion molecule expression, endothelial cell treatment with LPS plus S1P significantly enhanced adhesion of PBMCs under shear stress conditions compared with the effect of either ligand alone and exhibited comparable levels of cell adhesion strength as those after TNF-α treatment. Moreover, LPS and S1P cooperated to increase the expression of proinflammatory molecules such as IL-6, cyclooxygenase-2, and prostacyclin, as determined by ELISA and Western blot. The analysis of signaling pathways revealed the synergistic phosphorylation of ERK upon LPS plus S1P treatment of HUVEC and human aortic endothelial cells and cell-type differences on p38 and NF-κB activation. Moreover, pharmacological and small interfering RNA experiments disclosed the involvement of S1P1/3 and NF-κB in the cooperation effect and that cell origin determines the S1P receptors and signaling routes involved. Sphingosine kinase activity induction upon LPS plus S1P treatment suggests S1P– Sphingosine kinase axis involvement. In summary, LPS and S1P cooperate to increase proinflammatory molecules in endothelial cells and, in turn, to augment leukocyte adhesion, thus exacerbating S1P-mediated proadhesive/proinflammatory properties.

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Section: Discussionsupporting

confidence: 90%

Section: Real-time Rt-pcr Analysismentioning

confidence: 99%

Section: Immunodetection Of Icam-1 Cox-2 P-nf-kb and Mapksmentioning

confidence: 99%

“…Validated siRNA duplexes specific for S1P 1 and S1P 3 were as described (20). Quantitative PCR was performed to confirm downloading of human S1P receptors as described (20).…”

Section: Sirna Experimentsmentioning

confidence: 99%

See 2 more Smart Citations

Lipopolysaccharide and Sphingosine-1-Phosphate Cooperate To Induce Inflammatory Molecules and Leukocyte Adhesion in Endothelial Cells

Fernández‐Pisonero

Dueñas

Barreiro

et al. 2012

The Journal of Immunology

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“…In addition, peritoneal macrophages from FTY-treated mice displayed a decrease in classic proinflammatory M1 type macrophage activation induced by LPS and an increased anti-inflammatory M2 type macrophages activation induced by IL-4. This effect seems to be due to FTY-induced activation rather than downregulation of S1P receptors, as S1P or a specific agonist of S1P 1 (SEW2871) also blocked LPS-induced production of TNF, CCL2, IL-12, and inducible nitric-oxide synthetase 41,42) . Moreover, mature DCs generated in the presence of FTY showed an impaired immunostimulatory capacity and reduced IL-12 but increased IL-10 production, indicating a shift from Th1 toward Th2 differentiation 19) .…”

Section: Effect Of Fty On T Cellsmentioning

confidence: 97%

Therapy of autoimmune diseases by novel immunosuppressant FTY720

Tsunemi

Iwasaki

Miyazawa

et al. 2011

Inflammation and Regeneration

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The role of sphingosine 1 phosphate in coronary artery disease and ischemia reperfusion injury

Mihanfar

Nejabati

Fattahi

et al. 2018

Journal Cellular Physiology

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Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high‐density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein‐coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target.

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Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate

Cited by 47 publications

References 46 publications

Lipopolysaccharide and Sphingosine-1-Phosphate Cooperate To Induce Inflammatory Molecules and Leukocyte Adhesion in Endothelial Cells

Lipopolysaccharide and Sphingosine-1-Phosphate Cooperate To Induce Inflammatory Molecules and Leukocyte Adhesion in Endothelial Cells

Therapy of autoimmune diseases by novel immunosuppressant FTY720

The role of sphingosine 1 phosphate in coronary artery disease and ischemia reperfusion injury

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