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

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.

Danger-associated extracellular ATP counters MDSC therapeutic efficacy in acute GVHD

“…To confirm apyrase intraperitoneal injections limited MDSC-IL13 inflammasome conversion locally, MDSC-IL13s were generated from a novel reporter-transgenic donor strain, IDOL-tg, which has IL-1b promoter-driven luciferase expression in which IL-1b transcription and caspase-1 enzymatic processing are both required to yield a luminescent signal, whereas under noninflammasome conditions, IDOL proteasomal degradation prevents luminescence. 57 Under GVHD conditions, IDOL-MDSC-IL13s exhibited a robust signal, which was reduced by apyrase ( Figure 4E). On days 3, 5, and 7, MDSC-IL13 inflammasome activation was diminished by apyrase treatment (Figure 4E-F).…”

Suppression of inflammatory genes expression in the injured host intestinal wall during Mesocestoides vogae tetrathyridium larvae migration

“…In consequence to activation of the pathway, transcription factors such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) regulate transcription of IL-1β gene, and the transcription activates the production of a proIL-1β protein. ProIL-1β protein is secondly regulated via processing into mature IL-1β as an activated form by caspase-1, and is extracellularly secreted [ 37 – 39 ]. IL-1β binds to IL-1 receptors (IL-1Rs) on neutrophils, monocytes and macrophages and activates them.…”

Effects of the Cytoplasm and Mitochondrial Specific Hydroxyl Radical Scavengers TA293 and mitoTA293 in Bleomycin-Induced Pulmonary Fibrosis Model Mice

“…We purchased C57BL/6J mice from CLEA Japan, Inc. (Tokyo, Japan) and Keap1-based oxidative stress detector 48-transgenic (OKD48-Tg) and IL-1β-based dual-operating luciferase transgenic (IDOL-Tg) albino C57BL/6J mice from TransGenic Inc. (Kobe, Japan) [ 24 , 25 ]. Only 12-week-old male mice were used in the experiment.…”