- 作者：Bas Heinhuis ; Calin D. Popa ; Berry L.J.H. van Tits ; Soo-Hyun Kim ; Patrick L. Zeeuwen ; Wim B. van den Berg ; Jos W.M. van der Meer ; J. Adam van der Vliet ; Anton F.H. Stalenhoef ; Charles A. Dinarello ; Mihai G. Netea ; Leo A.B. Joosten
- 关键词：Cytokines ; Interleukin-32 ; TLR-ligands ; Matrix metalloproteinases ; Plaque instability
- 刊名：Cytokine
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：64
- 期：1
- 页码：433-440
- 全文大小：2255 K
Background
IL-32 has been previously shown to promote inflammation in rheumatoid arthritis patients and to contribute to IL-1¦Â-induced ICAM-1 as well as other proinflammatory cytokines synthesis in human umbilical endothelial cells (HUVECs). Given the high rate of atherosclerosis in RA, these observations suggest that IL-32 may be involved in the inflammatory pathways of atherosclerosis.Methods
mRNA and protein levels of IL-32 were determined in human atherosclerotic arterial vessel wall tissue by quantitative real-time PCR and immunohistochemistry. HUVEC and M1/M2 macrophages were stimulated with proinflammatory cytokines and TLR ligands to assess IL-32 mRNA induction. Human THP1 macrophages were transduced with AdIL-32¦Ã, to investigate induction of several proatherosclerotic mediators. Finally, aortas from IL-32¦Ã transgenic mice were studied and compared with aortas from age-matched wild-type mice.
Results
IL-32 expression was detectable in human atherosclerotic arterial vessel wall, with the expression of IL-32¦Â and IL-32¦Ã mRNA significantly enhanced. TLR3-ligand Poly I:C in combination with IFN¦Ã were the most potent inducers of IL-32 mRNA expression in both HUVEC and M1/M2 macrophages. Adenoviral overexpression of IL-32¦Ã in human THP1 macrophages resulted in increased production of CCL2, sVCAM-1, MMP1, MMP9, and MMP13. The IL-32¦Ã transgenic mice chow a normal fat diet exhibited vascular abnormalities resembling atherosclerosis.
Conclusions
IL-32 acts as a proinflammatory factor and may be implicated in the inflammatory cascade contributing to atherosclerosis. By promoting the synthesis of matrix metalloproteinases, it may further contribute to plaque instability. Further studies are warranted to investigate whether IL-32 may serve as a potential therapeutic target in fighting atherosclerosis.