Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines
Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/1463216 |
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| author | Bona Linke Yannick Schreiber Bettina Picard-Willems Patrick Slattery Rolf M. Nüsing Sebastian Harder Gerd Geisslinger Klaus Scholich |
| author_facet | Bona Linke Yannick Schreiber Bettina Picard-Willems Patrick Slattery Rolf M. Nüsing Sebastian Harder Gerd Geisslinger Klaus Scholich |
| author_sort | Bona Linke |
| collection | DOAJ |
| description | Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2 (PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF) α secretion out of the monocytes or macrophages. Platelet PGE2 mediated the upregulation of IL-10 in both cell types via the PGE2 receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFα synthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFα release. This platelet-mediated cross-regulation between PGE2 and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes. |
| format | Article |
| id | doaj-art-1f8495722a3c4c3a94bc72fd7164db46 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1f8495722a3c4c3a94bc72fd7164db462025-02-03T01:27:18ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/14632161463216Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and CytokinesBona Linke0Yannick Schreiber1Bettina Picard-Willems2Patrick Slattery3Rolf M. Nüsing4Sebastian Harder5Gerd Geisslinger6Klaus Scholich7Department of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Clinical Pharmacology, University Hospital Frankfurt, Frankfurt, GermanyPlatelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2 (PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF) α secretion out of the monocytes or macrophages. Platelet PGE2 mediated the upregulation of IL-10 in both cell types via the PGE2 receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFα synthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFα release. This platelet-mediated cross-regulation between PGE2 and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes.http://dx.doi.org/10.1155/2017/1463216 |
| spellingShingle | Bona Linke Yannick Schreiber Bettina Picard-Willems Patrick Slattery Rolf M. Nüsing Sebastian Harder Gerd Geisslinger Klaus Scholich Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines Mediators of Inflammation |
| title | Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines |
| title_full | Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines |
| title_fullStr | Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines |
| title_full_unstemmed | Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines |
| title_short | Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines |
| title_sort | activated platelets induce an anti inflammatory response of monocytes macrophages through cross regulation of pge2 and cytokines |
| url | http://dx.doi.org/10.1155/2017/1463216 |
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