IL‑37 expression is decreased in patients with hyperhomocysteinemia and protects cells from inflammatory injury by homocysteine

Wang,Sen; Huang,Zhen; Li,Wenrui; He,Suhui; Wu,Hongmei; Zhu,Jiandong; Li,Rumeng; Liang,Zhuangyan; Chen,Zhangquan

doi:10.3892/mmr.2019.10804

IL‑37 expression is decreased in patients with hyperhomocysteinemia and protects cells from inflammatory injury by homocysteine

Authors:
- Sen Wang
- Zhen Huang
- Wenrui Li
- Suhui He
- Hongmei Wu
- Jiandong Zhu
- Rumeng Li
- Zhuangyan Liang
- Zhangquan Chen
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Affiliations: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China, Longgang Central Hospital, Shenzhen, Guangdong 518116, P.R. China, Eighth People's Hospital of Dongguan City, Dongguan, Guangdong 523321, P.R. China
Published online on: November 6, 2019 https://doi.org/10.3892/mmr.2019.10804
Pages: 371-378

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Abstract

As a novel anti‑inflammatory cytokine of the interleukin (IL)‑1 family, IL‑37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL‑37 in hHcy. In the present study, the levels of cytokines including IL‑37, IL‑1β, IL‑6 and tumor necrosis factor‑α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription‑quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK‑8 kit. In the present study, mean serum IL‑37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL‑37 mRNA expression was 73.5% lower (P<0.01) and IL‑37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of IL‑37 in PBMCs in vitro. In 293T cells, overexpression of IL‑37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL‑1β, IL‑6 and tumor necrosis factor‑α. In conclusion, IL‑37 was downregulated by Hcy in vivo and in vitro, and IL‑37 exhibited a protective role against cell injury induced by Hcy.

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