Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFKB signalling pathway in monocytes
| العنوان: | Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFKB signalling pathway in monocytes |
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| المؤلفون: | Qiang Chen, Karlheinz Peter, Zhou Zhou, Song Peng, Jun Jie Bei, Xiao Long Qu, Zheng Ping Yu, Hou Yuan Hu, Chuan Liu, Cheng Hai Liu, Wei Bo Zhao |
| المصدر: | Thrombosis and Haemostasis. 115:632-645 |
| بيانات النشر: | Georg Thieme Verlag KG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Blood Platelets, 0301 basic medicine, Staphylococcus aureus, Interleukin-1beta, Active Transport, Cell Nucleus, Inflammation, 030204 cardiovascular system & hematology, Monocytes, Receptors, Tumor Necrosis Factor, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Cell Movement, Cell-Derived Microparticles, Humans, Medicine, Platelet, Gene Silencing, Platelet activation, CD40 Antigens, RNA, Small Interfering, Chemokine CCL2, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha, business.industry, Activator (genetics), Monocyte, Intracellular Signaling Peptides and Proteins, NF-kappa B p50 Subunit, Hematology, Flow Cytometry, Recombinant Proteins, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, Immunology, RNA Interference, Tumor necrosis factor alpha, medicine.symptom, Signal transduction, business, Signal Transduction |
| الوصف: | SummaryPathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation. |
| تدمد: | 2567-689X 0340-6245 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c3f92fda2c77162bcb106a8fcdfc1b8Test https://doi.org/10.1160/th15-04-0322Test |
| رقم الانضمام: | edsair.doi.dedup.....7c3f92fda2c77162bcb106a8fcdfc1b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2567689X 03406245 |
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