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Calcium phosphate particles stimulate interleukin-1ß release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release.
Dautova, Yana; Kapustin, Alexander N; Pappert, Kevin; Epple, Matthias; Okkenhaug, Hanneke; Cook, Simon J; Shanahan, Catherine M; Bootman, Martin D; Proudfoot, Diane.
Afiliação
  • Dautova Y; Signalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
  • Kapustin AN; Cardiovascular Division, James Black Centre, King's College London,125 Coldharbour Lane, London SE5 9NU, UK.
  • Pappert K; Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Essen-Duisburg, Essen 45117, Germany.
  • Epple M; Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Essen-Duisburg, Essen 45117, Germany.
  • Okkenhaug H; Signalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
  • Cook SJ; Signalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
  • Shanahan CM; Cardiovascular Division, James Black Centre, King's College London,125 Coldharbour Lane, London SE5 9NU, UK.
  • Bootman MD; School of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK.
  • Proudfoot D; Signalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK. Electronic address: diane.proudfoot@babraham.ac.uk.
J Mol Cell Cardiol ; 115: 82-93, 2018 02.
Article em En | MEDLINE | ID: mdl-29274344
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-1ß (IL-1ß). 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-1ß release from VSMCs, we demonstrated that CaP particles stimulated IL-1ß release from proliferating and senescent human VSMCs, but with substantially greater IL-1ß 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-1ß 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-1ß 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-1ß and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1ß 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-1ß release. CONCLUSIONS: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1ß, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and pro-calcific potential of microcalcification.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatos de Cálcio / Miócitos de Músculo Liso / Interleucina-1beta / Exossomos / Quinase Syk / Músculo Liso Vascular Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatos de Cálcio / Miócitos de Músculo Liso / Interleucina-1beta / Exossomos / Quinase Syk / Músculo Liso Vascular Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article