Transgenic mouse model for imaging of interleukin-1β-related inflammation in vivo.
Transgenic mouse model for imaging of interleukin-1β-related inflammation in vivo.
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DOI：
10.1038/srep17205
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发表时间：
2015-11-24
影响因子：
4.6
通讯作者：
Yamamura K
中科院分区：
文献类型：
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作者：
Iwawaki T;Akai R;Oikawa D;Toyoshima T;Yoshino M;Suzuki M;Takeda N;Ishikawa TO;Kataoka Y;Yamamura K
炎症是与各种疾病的症状相关的生物反应，其研究对于了解此类疾病的病理状况以及制定促进愈合的战略计划非常重要。因此，开发用于检测炎症状况的技术至关重要。白细胞介素-1 β（IL-1β）是一种主要由单核细胞和巨噬细胞在炎症刺激下产生和分泌的促炎细胞因子。IL-1β的激活通过启动子的转录诱导和炎性小体的翻译后加工来调节。在这里，我们开发了一种报告基因，通过使用双重调节系统来监测IL-1β的激活状态，并且通过使用报告基因，我们建立了一种允许低侵入性可视化炎症状态的小鼠模型。先前依赖于IL-1β转录或加工的报告系统在背景噪声或信号特异性方面显示出问题。我们的报告系统通过结合启动子调控和IL-1β加工的优点克服了这些缺点。我们的小鼠模型分别检测到由肝炎或胰腺炎模型引起的肝脏和胰腺中的特异性生理炎症。因此，我们的报告基因和小鼠模型有望成为未来医学科学的有用生物资源。
Inflammation is a biological response associated with symptoms of various diseases, and its study is important in gaining an understanding of the pathological conditions of such diseases and in making strategic plans for promoting healing. It is therefore essential to develop technologies for the detection of inflammatory conditions. Interleukin-1β (IL-1β) is a proinflammatory cytokine produced and secreted mainly by monocytes and macrophages in response to inflammatory stimulation. The activation of IL-1β is regulated through transcriptional induction by the promoter and post-translational processing by the inflammasome. Here we have developed a reporter gene to monitor the activation status of IL-1β by using a dual regulation system and, by using the reporter gene, we have established a mouse model that permits low-invasive visualization of the inflammatory status. Previous reporter systems dependent on the transcription or processing of IL-1β show problems in terms of background noise or signal specificity. Our reporter system overcomes these weaknesses by combining advantages from regulation by a promoter and processing of IL-1β. Our mouse model detected specific physiological inflammation in the liver and pancreas caused by hepatitis or pancreatitis models, respectively. Our reporter gene and mouse model are therefore expected to become useful bioresources for future medical science.