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Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3 inflammasome activation

AIM: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLR...

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Detalles Bibliográficos
Autores principales: Gregersen, Ida, Sandanger, Øystein, Askevold, Erik T., Sagen, Ellen Lund, Yang, Kuan, Holm, Sverre, Pedersen, Turid M., Skjelland, Mona, Krohg-Sørensen, Kirsten, Hansen, Trond Vidar, Dahl, Tuva Børresdatter, Otterdal, Kari, Espevik, Terje, Aukrust, Pål, Yndestad, Arne, Halvorsen, Bente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703457/
https://www.ncbi.nlm.nih.gov/pubmed/29176764
http://dx.doi.org/10.1371/journal.pone.0188387
Descripción
Sumario:AIM: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro. METHODS: Plasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27 and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques from patients and in non-atherosclerotic vessels. THP-1 monocytes, primary monocytes and peripheral blood mononuclear cells (PBMCs) were used to study effects of IL-27 in vitro. RESULTS: Our main findings were: (i) Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R was significantly elevated in plaques compared to control vessels, and co-localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome activation in monocytes with enhanced release of IL-1 β. CONCLUSIONS: We demonstrate increased levels of IL-27 and IL-27R in patients with carotid atherosclerosis. Our in vitro findings suggest an inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.