Interleukin 6 regulates psoriasiform inflammation–associated thrombosis
Yunmei Wang, … , Thomas S. McCormick, Nicole L. Ward
Yunmei Wang, … , Thomas S. McCormick, Nicole L. Ward
Published December 8, 2016
Citation Information: JCI Insight. 2016;1(20):e89384. https://doi.org/10.1172/jci.insight.89384.
View: Text | PDF
Research Article Cardiology Dermatology

Interleukin 6 regulates psoriasiform inflammation–associated thrombosis

Abstract

Psoriasis patients are at increased risk of heart attack and stroke and have elevated MRP8/14 levels that predict heart attack. The KC-Tie2 psoriasiform mouse model exhibits elevated MRP8/14 and is prothrombotic. Mrp14–/– mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2xMrp14–/– mice remain prothrombotic. Treating KC-Tie2xMrp14–/– mice with anti–IL-23p19 antibodies reversed the skin inflammation, improved thrombosis, and decreased IL-6. In comparison, IL-6 deletion from KC-Tie2 animals improved thrombosis despite sustained skin inflammation, suggesting that thrombosis improvements following IL-23 inhibition occur secondary to IL-6 decreases. Psoriasis patient skin has elevated IL-6 and IL-6 receptor is present in human coronary atheroma, supporting a link between skin and distant vessel disease in patient tissue. Together, these results identify a critical role for skin-derived IL-6 linking skin inflammation with thrombosis, and shows that in the absence of IL-6 the connection between skin inflammation and thrombosis comorbidities is severed.

Authors

Yunmei Wang, Jackelyn B. Golden, Yi Fritz, Xiufen Zhang, Doina Diaconu, Maya I. Camhi, Huiyun Gao, Sean M. Dawes, Xianying Xing, Santhi K. Ganesh, Johann E. Gudjonsson, Daniel I. Simon, Thomas S. McCormick, Nicole L. Ward

×

Figure 2

Proinflammatory cytokines increase in KC-Tie2xMrp14–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Proinflammatory cytokines increase in KC-Tie2xMrp14–/– mice. Transcript ...
Transcript levels of (A) IL-12/23p40, (B) IL-17A, and (C) IL-6 measured using qRT-PCR in control (n = 9), KC-Tie2 (n = 9), Mrp14–/– (n = 13), and KC-Tie2xMrp14–/– (n = 12) mice. Protein levels (pg/ml) measured using ELISA for (D) IL-12/23p40, (E) IL-17A, and (F) IL-6 in skin of control (n = 7), KC-Tie2 (n = 9), Mrp14–/– (n = 13), and KC-Tie2xMrp14–/– (n = 11) mice. Values shown represent the mean ± SEM. Each dot represents 1 individual mouse. qRT-PCR data were analyzed using a nonparametric Mann-Whitney U test. ELISA data were analyzed using a Student’s t test. P values are as indicated.