Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Marrache, Anne Marilise; Gobeil, Fernand; Bernier, Sylvie G.; Staňková, Jana; Rola‐Pleszczynski, Marek; Choufani, Sanaa; Bkaily, Ghassan; Bourdeau, Annie; Sirois, Martin G.; Vazquez-Tello, Alejandro; Fan, Li; Joyal, Jean‐Sébastien; Filep, János G.; Varma, Daya R.; Ribeiro‐da‐Silva, Alfredo; Chemtob, Sylvain

doi:10.4049/jimmunol.169.11.6474

Cited by 113 publications

(94 citation statements)

References 64 publications

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“…For instance, the receptors for platelet-activating factor, prostaglandin E 2 , and lysophosphatidic acid (43,45) are located in the nucleus constitutively. These receptors are thought to be activated by endogenously produced, nonsecreted ligands.…”

Section: C3a and C5a Are Chemotactic Factors For Human Mesenchymal Stmentioning

confidence: 99%

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Schraufstätter

DiScipio

Zhao

et al. 2009

The Journal of Immunology

164

136

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Mesenchymal stem cells (MSCs) have a great potential for tissue repair, especially if they can be delivered efficiently to sites of tissue injury. Since complement activation occurs whenever there is tissue damage, the effects of the complement activation products C3a and C5a on MSCs were examined. Both C3a and C5a were chemoattractants for human bone marrow-derived MSCs, which expressed both the C3a receptor (C3aR) and the C5a receptor (C5aR; CD88) on the cell surface. Specific C3aR and C5aR inhibitors blocked the chemotactic response, as did pertussis toxin, indicating that the response was mediated by the known anaphylatoxin receptors in a Gi activation-dependent fashion. While C5a causes strong and prolonged activation of various signaling pathways in many different cell types, the response observed with C3a is generally transient and weak. However, we show herein that in MSCs both C3a and C5a caused prolonged and robust ERK1/2 and Akt phosphorylation. Phospho-ERK1/2 was translocated to the nucleus in both C3a and C5a-stimulated MSCs, which was associated with subsequent phosphorylation of the transcription factor Elk, which could not be detected in other cell types stimulated with C3a. More surprisingly, the C3aR itself was translocated to the nucleus in C3a-stimulated MSCs, especially at low cell densities. Since nuclear activation/translocation of G protein-coupled receptors has been shown to induce long-term effects, this novel observation implies that C3a exerts far-reaching consequences on MSC biology. These results suggest that the anaphylatoxins C3a and C5a present in injured tissues contribute to the recruitment of MSCs and regulation of their behavior.

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Section: C3a and C5a Are Chemotactic Factors For Human Mesenchymal Stmentioning

confidence: 99%

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Schraufstätter

DiScipio

Zhao

et al. 2009

The Journal of Immunology

164

136

View full text Add to dashboard Cite

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“…18 Rat retinas were pooled 3,4 and membranous and cytosolic fractions were separated as previously described. 21 Antibodies used were polyclonal anti-COX-2 (Cayman); polyclonal anti-COX-1 (Santa Cruz Biotechnology); mouse monoclonal EP 2 , EP 3 , and EP 4 (Exalpha Biologicals); polyclonal anti-VEGF antibody (Chemicon); rat monoclonal anti-VEGF receptor (VEGFR)-2 (Chemicon); monoclonal anti-TSP-1 (Oncogene); polyclonal purified anti-CD36; monoclonal …”

Section: Western Blotmentioning

confidence: 99%

Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy

Valamanesh²,

et al. 2003

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Background-Intravitreal neovascular diseases, as in ischemic retinopathies, are a major cause of blindness. Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)-2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy. Methods and Results-We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E 2 , mainly via its prostaglandin E receptor 3 (EP 3 ), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP 3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36. Conclusion-These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.

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“…5A). When cells were pretreated with CD, PAF-induced IP production was significantly reduced for PAF concentrations ranging from 1 to 1000 nM, and the EC 50 was markedly shifted to the right. CHO cells stably expressing human PAFR were also used to determine the effect of lipid raft disruption on PAF-induced IP production (Fig.…”

Section: Integrity Of Caveolae/rafts Is Important For Paf-induced Ip mentioning

confidence: 99%

Caveolae Facilitate but Are Not Essential for Platelet-Activating Factor-Mediated Calcium Mobilization and Extracellular Signal-Regulated Kinase Activation

Poisson

Rollin

Véronneau

et al. 2009

The Journal of Immunology

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Certain proteins, including receptors and signaling molecules, are known to be enriched in caveolae and lipid rafts. Caveolin-1, the major structural protein of caveolae, specifically interacts with many signaling molecules and, thus, caveolae and lipid rafts are often seen as preassembled signaling platforms. A potential binding site for caveolin-1 is present in the platelet-activating factor receptor (PAFR) sequence, and many downstream signaling components of PAFR activation preferentially localize in caveolae. The aim of this study was to investigate whether the PAFR was localized in caveolae/lipid raft domains and, if so, what would be the significance of such localization for PAFR signaling. In this study, we demonstrate that PAFR localizes within membrane microdomains, in close proximity to caveolin-1 in living cells, with potential interaction through a caveolin-1-binding sequence in the PAFR C terminus. Caveolin-1, however, is not essential for PAFR localization in lipid rafts. Disruption of caveolae/lipid rafts with methyl-β-cyclodextrin markedly reduced PAF-triggered inositol phosphate production and cytosolic calcium flux, suggesting that PAFR signaling through the Gαq protein was critically dependent on integrity of lipid rafts and/or caveolae. Interestingly, whereas in caveolin-1-expressing cells lipid raft disruption markedly decreased PAFR-mediated activation of the ERK/MAPK pathway, in cells lacking caveolae, such as leukocytes, lipid raft disruption had either the same inhibitory effect (Ramos B cells) or no effect (monocytes) on PAFR capacity to signal through the ERK/MAPK pathway. In conclusion, PAFR appears to localize within caveolae or lipid rafts in different cell types, and this location may be important for specific signaling events.

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Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Cited by 113 publications

References 64 publications

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy

Caveolae Facilitate but Are Not Essential for Platelet-Activating Factor-Mediated Calcium Mobilization and Extracellular Signal-Regulated Kinase Activation

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