바로가기  >

Abstract
Inflammasome plays a critical role in diverse inflammatory disorders, including cancers and Alzheimer's disease. It is induced by various pathogenic insults and activates caspase-1, a hallmark executor of inflammasome. Here, we developed an activatable fluorescence probe for visualization of active caspase-1. This caspase-1 probe is biocompatible, efficiently delivered into cells and tissues, and specifically emits fluorescence upon caspase-1 activation as assessed in in vitro and in vivo models of inflammatory conditions. We demonstrated efficient in vivo imaging of caspase-1 activation in early stages of various inflammatory conditions of mice models, including endotoxin shock, inflammatory bowel disorder, transplanted cancer, and Alzheimer's disease. Notably, the caspase-1 probe enables detection of neuroinflammation in vivo two months earlier than cognitive impairments occur in Alzheimer's disease model. We detected significant fluorescence emitted from inflamed sites, as well as their draining lymph nodes, by macroscopic imaging analysis within 30 min after systemic injection of the probe. This novel synthetic probe could be applied for efficient and rapid detection of caspase-1 activity in a spatiotemporal way by non-invasive imaging.

Author information

Ko YJ1, Lee JW2, Yang EJ3, Jang N2, Park J4, Jeon YK5, Yu JW6, Cho NH7, Kim HS8, Chan Kwon I9.
1
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
2
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Department of Pharmacology, Seoul National University, College of Medicine, Seoul, 03080, Republic of Korea.
4
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
5
Department of Pathology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
6
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 03722, South Korea.
7
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, 03080, South Korea. Electronic address: chonh@snu.ac.kr.
8
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Department of Pharmacology, Seoul National University, College of Medicine, Seoul, 03080, Republic of Korea; Seoul National University College of Medicine, Bundang Hospital, Sungnam, 13620, Republic of Korea. Electronic address: hyisun@snu.ac.kr.
9
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; KIST-DFCI On-Site-Lab, Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA. Electronic address: ikwon@kist.re.kr.

이달의 연구자 바로가기