Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release
| العنوان: | Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release |
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| المؤلفون: | Matthias Epple, Yana Dautova, Kevin Pappert, Alexander N. Kapustin, Martin D. Bootman, Hanneke Okkenhaug, Diane Proudfoot, Simon J. Cook, Catherine M. Shanahan |
| المصدر: | Journal of Molecular and Cellular Cardiology Dautova, Y, Kapustin, A, Pappert, K, Epple, M, Okkenhaug, H, Cook, S J, Shanahan, C M, Bootman, M D & Proudfoot, D 2017, ' Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells : A role for spleen tyrosine kinase and exosome release ', Journal of Molecular and Cellular Cardiology . https://doi.org/10.1016/j.yjmcc.2017.12.007Test |
| بيانات النشر: | Academic Press, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Calcium Phosphates, Male, BM, basal culture medium, Vascular smooth muscle, Inflammasomes, Interleukin-1beta, Syk, Exosomes, Muscle, Smooth, Vascular, SYK, Phosphorylation, Cells, Cultured, Caspase 1, Inflammasome, Middle Aged, CaP, calcium phosphate, Cell biology, VSMC, vascular smooth muscle cells, Caspase-1, Cytokines, LPS, lipopolysaccharide, Female, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, IL-1β, interleukin-1β, ATP, adenosine triphosphate, Myocytes, Smooth Muscle, Chemie, chemistry.chemical_element, Calcium, Exosome, MSU, monosodium urate, Article, SYK, spleen tyrosine kinase, 03 medical and health sciences, Young Adult, medicine, SFM, serum-free medium, Humans, Syk Kinase, Secretion, NLRP3: nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3, Molecular Biology, Calcium phosphate particles, Enzyme Activation, 030104 developmental biology, chemistry |
| الوصف: | Aims Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and pro-calcific potential of microcalcification. Graphical abstract Image 2 Highlights • CaP particles induce IL-1β release from human VSMCs. • Senescent cells display higher basal and CaP-stimulated IL-1β release. • Inflammasome agonists ATP, nigericin and MSU crystals do not induce IL-1β release from human VSMCs. • CaP particle-induced IL-1β release is dependent on SYK, caspase-1 and exosome release. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1095-8584 0022-2828 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d86e001074dcd1dcf16d9ed519a5db8Test http://europepmc.org/articles/PMC5823844Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0d86e001074dcd1dcf16d9ed519a5db8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10958584 00222828 |
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