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首页> 外文期刊>Journal of Translational Medicine >Physiological and molecular effects of interleukin-18 administration on the mouse kidney
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Physiological and molecular effects of interleukin-18 administration on the mouse kidney

机译：白细胞介素18给药对小鼠肾脏的生理和分子影响

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The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy. Before clinical application, the effects of interleukin-18 on the kidney need to be determined. In the current study, we examined the kidney of interleukin-18 knockout (Il18?/?) mice and the effects of interleukin-18 on the kidney following intravenous administration of recombinant interleukin-18. Il18?/? male mice were generated on the C57Bl/6 background and littermate C57Bl/6 Il18+/+ male mice were used as controls. To assess kidney damage, serum creatinine and blood urea nitrogen levels were measured and histopathological analysis was performed. For molecular analysis, microarray and quantitative reverse transcription PCR was performed using mice 6 and 12?weeks old. To evaluate the short- and long-term effects of interleukin-18 on the kidney, recombinant interleukin-18 was administered for 2 and 12?weeks, respectively. Compared with Il18+/+ mice, Il18?/? mice developed kidney failure in their youth-6?weeks of age, but the condition was observed to improve as the mice aged, even though dyslipidemia, arteriosclerosis, and higher insulin resistance occurred. Analyses of potential molecular mechanisms involved in the onset of early kidney failure in Il18?/? mice identified a number of associated genes, such as Itgam, Nov, and Ppard. Intravenous administration of recombinant interleukin-18 over both the short and long term showed no effects on the kidney despite significant improvement in metabolic diseases. Short- and long-term administration of interleukin-18 appeared to have no adverse effects on the kidney in these mice, suggesting that administration may be a safe and novel treatment for metabolic diseases and cancer.
机译：细胞因子白细胞介素18最初被确定为诱导干扰素γ的促炎因子。但是，越来越多的证据表明它对生理功能具有非免疫作用。我们先前研究了白介素18与血脂异常，非酒精性脂肪肝疾病和非酒精性脂肪性肝炎之间的潜在病理生理关系，并建议白介素18作为一种可能的新疗法，不仅适用于这些疾病，还适用于癌症免疫治疗。在临床应用之前，需要确定白介素18对肾脏的作用。在当前的研究中，我们检查了静脉注射重组白介素18后白介素18基因敲除（Il18α/β）小鼠的肾脏以及白介素18对肾脏的影响。 Il18？/？在C57Bl / 6背景上产生雄性小鼠，并将同窝的C57Bl / 6 Il18 + / +雄性小鼠用作对照。为了评估肾脏损害，测量了血清肌酐和血液尿素氮水平，并进行了组织病理学分析。为了进行分子分析，使用了6周和12周龄的小鼠进行了微阵列和定量逆转录PCR。为了评估白介素18对肾脏的短期和长期作用，分别给予重组白介素18 2周和12周。与Il18 + / +小鼠相比，Il18？/？小鼠在6周龄时出现肾脏衰竭，但是即使血脂异常，动脉硬化和较高的胰岛素抵抗发生，随着年龄的增长，病情也会改善。 Il18α/β早期肾衰竭发作的潜在分子机制分析小鼠鉴定了许多相关基因，例如Itgam，Nov和Ppard。尽管代谢性疾病明显改善，短期和长期静脉内注射重组白介素18均未显示对肾脏有影响。短期和长期给予白介素18似乎对这些小鼠的肾脏没有不良影响，这表明给药可能是一种代谢疾病和癌症的安全而新颖的治疗方法。

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