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High and fluctuating glucose levels increase the expression and secretion of interleukin18 in mouse peritoneal macrophages

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Macrophages are involved in the progression of atherosclerosis by releasing proinflammatory 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 IL18, and high and fluctuating glucose levels in mouse peritoneal macrophages (MPMs), and to assess the involvement of the cJun Nterminal 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 IL18 were detected using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and ELISA, respectively. High levels of glucose increased the expression and secretion levels of IL18 in a dosedependent 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 (RTqPCR, 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 IL18 increased 8 and 12 h following exposure to highglucose, and then decreased at 18 h (P<0.05, vs. 3 h). Furthermore, SP600125, a JNK inhibitor, decreased the highglucoseinduced gene expression of IL18 in a dosedependent manner. Therefore, high and fluctuating levels of glucose may be associated with inflammation and diabetic atherosclerosis by regulating the expression levels of IL18. The present study identified the JNK signaling pathway as one of the mechanisms underlying this association. Targeting IL18 may be a novel therapeutic approach against diabetesassociated atherosclerosis.
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Document Type: Research Article

Affiliations: 1: Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233020, P.R. China 2: Department of Pathology, Bengbu Medical College, Bengbu, Anhui 233020, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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