High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages

Zhang,Chenchen; Bi,Yaxin; Jin,Guoxi; Gan,Huaiyong; Yu,Lei

doi:10.3892/mmr.2015.3753

High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages

Authors:
- Chenchen Zhang
- Yaxin Bi
- Guoxi Jin
- Huaiyong Gan
- Lei Yu
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Affiliations: Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233020, P.R. China, Department of Pathology, Bengbu Medical College, Bengbu, Anhui 233020, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3753
Pages: 2715-2720

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Abstract

Macrophages are involved in the progression of atherosclerosis by releasing pro‑inflammatory cytokines. High levels of interleukin (IL)‑18 are associated with an increased risk of developing diabetes and atherosclerosis. The present study aimed to investigate the association between IL‑18, and high and fluctuating glucose levels in mouse peritoneal macrophages (MPMs), and to assess the involvement of the c‑Jun N‑terminal kinase (JNK) pathway in this association. The MPMs were exposed to 4, 8, 16, 24 and 32 mM glucose for 6 h, which was alternated to either 4/24 mM glucose every 1.5 h for 6 h, or to 32 mM glucose for 3, 6, 12 and 18 h. The expression and secretion levels of IL‑18 were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and ELISA, respectively. High levels of glucose increased the expression and secretion levels of IL‑18 in a dose‑dependent manner (P<0.05, vs. 4 mM glucose). This increase was more important in the cells exposed to fluctuating 4/24 mM glucose every 1.5 h compared with the cells exposed to stable 24 mM glucose (RT‑qPCR, 0.78±0.05, vs. 0.66±0.07; ELISA, 188.23±20.32, vs. 143.16±13.07 pg/ml; P<0.05). The expression and secretion levels of IL‑18 increased 8 and 12 h following exposure to high‑glucose, and then decreased at 18 h (P<0.05, vs. 3 h). Furthermore, SP600125, a JNK inhibitor, decreased the high‑glucose‑induced gene expression of IL‑18 in a dose‑dependent manner. Therefore, high and fluctuating levels of glucose may be associated with inflammation and diabetic atherosclerosis by regulating the expression levels of IL‑18. The present study identified the JNK signaling pathway as one of the mechanisms underlying this association. Targeting IL‑18 may be a novel therapeutic approach against diabetes‑associated atherosclerosis.

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