Transgenic mouse model for imaging of interleukin-1β-related inflammation in vivo

用于体内白细胞介素-1β相关炎症成像的转基因小鼠模型

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作者:Takao Iwawaki, Ryoko Akai, Daisuke Oikawa, Takae Toyoshima, Mayuko Yoshino, Mitsumi Suzuki, Naoki Takeda, Tomo-o Ishikawa, Yosky Kataoka, Ken-ichi Yamamura

Abstract

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.

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