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Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.

ABSTRACT: Tissue factor (TF) is the primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation when released upon plaque rupture. Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells (ECs). Here, we investigated the impact of IL-33 on TF in human ECs, as a possible new link between inflammation and coagulation. IL-33 induced TF mRNA and protein in human umbilical vein ECs and coronary artery ECs. IL-33-induced TF expression was ST2- and NF-?B-dependent, but IL-1-independent. IL-33 also increased cell surface TF activity in ECs and TF activity in ECs-derived microparticles. IL-33-treated ECs reduced coagulation time of whole blood and plasma but not of factor VII-deficient plasma. In human carotid atherosclerotic plaques (n?=?57), TF mRNA positively correlated with IL-33 mRNA expression (r?=?0.691, p?

SUBMITTER: Stojkovic S

PROVIDER: S-EPMC4855148 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.

Stojkovic Stefan S Kaun Christoph C Basilio Jose J Rauscher Sabine S Hell Lena L Krychtiuk Konstantin A KA Bonstingl Cornelia C de Martin Rainer R Gröger Marion M Ay Cihan C Holnthoner Wolfgang W Eppel Wolfgang W Neumayer Christoph C Huk Ihor I Huber Kurt K Demyanets Svitlana S Wojta Johann J

Scientific reports 20160504

Tissue factor (TF) is the primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation when released upon plaque rupture. Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells (ECs). Here, we investigated the impact of IL-33 on TF in human ECs, as a possible new link between inflammation and coagulation. IL-33 induced TF mRNA and protein in human umbilical vein ECs and cor ...[more]

PMID: 27142573

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Project description:IntroductionInterleukin-33 (IL-33), the ligand for the receptor ST2, is abundant in adipose tissue, including preadipocytes, adipocytes, and endothelial cells. The IL-33/ST2 axis is protective against obesity, insulin resistance, and type 2 diabetes (T2D) in animal models. We determined whether adipose tissue IL-33 was associated with glycated hemoglobin (HbA1c), as well as mediators of inflammation and immune regulation and beiging of adipose tissue, among individuals with varying degrees of glycemia.Materials and methodsA total of 91 adults with normoglycemia, prediabetes, and T2D were included. After measuring their anthropometric and biochemical parameters, subcutaneous adipose tissue samples were isolated and mRNA expression of cytokines, chemokines, chemokine receptors, pattern recognition receptors, and mediators involved in beiging of adipose tissue were measured.ResultsAdipose tissue IL-33 was inversely associated with HbA1c in individuals with normoglycemia and T2D but not in those with prediabetes and was inversely correlated with fasting plasma glucose in individuals with T2D and with a better glycemic control. IL-33-to-ST2 ratio was inversely correlated with HbA1c in individuals with normoglycemia but not in those with prediabetes or T2D. IL-33 was directly associated with ST2, CD302, fibrinogen-like protein 2 (FGL2), and PR domain containing 16 (PRDM16) but inversely correlated with chemokine (C-C motif) ligand (CCL) 7 and CCL8 in individuals with normoglycemia. Similarly, IL-33 was directly associated with ST2, CD302, FGL2, PRDM16, and, additionally, toll-like receptor (TLR) 3 and IL-12A in individuals with T2D. However, IL-33 was not associated with any of these mediators but was directly and strongly associated with TLR9 in individuals with prediabetes.ConclusionsIL-33 and/or IL-33/ST2 dynamics and biological functions may play a role in overall glycemia among humans and may represent a novel target by which glucose-lowering managements confer their beneficial effects.

Dataset Information

Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.

Publications

Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.

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