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

白细胞介素 27 在颈动脉粥样硬化中增加并促进 NLRP3 炎症小体活化

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作者:Ida Gregersen, Øystein Sandanger, Erik T Askevold, Ellen Lund Sagen, Kuan Yang, Sverre Holm, Turid M Pedersen, Mona Skjelland, Kirsten Krohg-Sørensen, Trond Vidar Hansen, Tuva Børresdatter Dahl, Kari Otterdal, Terje Espevik, Pål Aukrust, Arne Yndestad, Bente Halvorsen

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.

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.

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.

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