Towards a role of interleukin-32 in atherosclerosis
SourceCytokine, 64, 1, (2013), pp. 433-40
Article / Letter to editor
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SubjectIGMD 5: Health aging / healthy living NCEBP 14: Cardiovascular diseases; N4i 1: Pathogenesis and modulation of inflammation; N4i 1: Pathogenesis and modulation of inflammation NCEBP 14: Cardiovascular diseases; N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; NCEBP 14: Cardiovascular diseases NCMLS 3: Tissue engineering and pathology; NCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapy
BACKGROUND: IL-32 has been previously shown to promote inflammation in rheumatoid arthritis patients and to contribute to IL-1beta-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-32gamma, to investigate induction of several proatherosclerotic mediators. Finally, aortas from IL-32gamma 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-32beta and IL-32gamma mRNA significantly enhanced. TLR3-ligand Poly I:C in combination with IFNgamma were the most potent inducers of IL-32 mRNA expression in both HUVEC and M1/M2 macrophages. Adenoviral overexpression of IL-32gamma in human THP1 macrophages resulted in increased production of CCL2, sVCAM-1, MMP1, MMP9, and MMP13. The IL-32gamma 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.
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