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Interleukin-32? Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis.

ABSTRACT: Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32? in vascular inflammation and atherogenesis has not been studied. Methods: IL-32? function was assessed in cells with transient IL-32? overexpression or treated with recombinant human IL-32? by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively. In addition, the participation of IL-32? on vascular inflammation, arterial wall thickening, and atherosclerosis in vivo was monitored in human IL-32? transgenic (hIL-32?-Tg) mice with or without ApoE knockout (ApoE ^-/- /hIL-32?-Tg). Results: Our analyses showed that IL-32? suppresses genes involved in the inflammatory and immune responses and cell proliferation, and by limiting matrix metalloproteinase (MMP) function. In vivo, administration of hIL-32? inhibited vascular inflammation and atherosclerosis in hIL-32?-Tg and ApoE ^-/- /hIL-32?-Tg mice. Subsequent microarray and in silico analysis also revealed a marked decreased in inflammatory gene expression in hIL-32?-Tg mice. Collectively, our studies demonstrated that IL-32? upregulates the atheroprotective genes Timp3 and Reck by downregulating microRNA-205 through regulation of the Rprd2-Dgcr8/Ddx5-Dicer1 biogenesis pathway. Conclusion: Our findings provide the first direct evidence that IL-32? is an anti-inflammatory and anti-atherogenic cytokine that may be useful as a diagnostic and therapeutic protein in atherosclerosis.

SUBMITTER: Son DJ

PROVIDER: S-EPMC5505053 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis.

Son Dong Ju DJ Jung Yu Yeon YY Seo Young Sik YS Park Heonyong H Lee Dong Hun DH Kim Sanghyeon S Roh Yoon-Seok YS Han Sang Bae SB Yoon Do Young DY Hong Jin Tae JT

Theranostics 20170601 8

Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied. <b><i>Methods:</i></b> IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA ex ...[more]

PMID: 28740544

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Dataset Information

Interleukin-32? Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis.

Publications

Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis.

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