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Updated: May 20, 2025
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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
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CRM1 mediates ASC nuclear export and inflammasome activation
Rui Cao1, Bolong Lin1, Hongbin He1
1National Key Laboratory of immune response and immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China.
International Immunopharmacology
|March 26, 2025
Summary
Chromosome region maintenance 1 (CRM1) facilitates inflammasome activation by enabling adaptor protein ASC nuclear export. Inhibiting CRM1 reduces inflammasome activity and alleviates autoimmune disease symptoms in mice.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Inflammasomes are critical innate immune sensors involved in inflammatory diseases.
- Adaptor protein ASC's nuclear-cytosolic translocation is key for inflammasome activation, but the mechanism is unknown.
Purpose of the Study:
- To elucidate the mechanism of ASC translocation and its role in inflammasome activation.
- To investigate the therapeutic potential of targeting this mechanism in inflammatory diseases.
Main Methods:
- Utilized pharmacological inhibition and genetic deletion of CRM1 in macrophages.
- Investigated inflammasome activation (NLRP3, AIM2, NLRC4, pyrin) and ASC nuclear export.
- Assessed disease severity in a mouse model of experimental autoimmune encephalomyelitis (EAE).
Main Results:
- CRM1 inhibition or deletion significantly suppressed inflammasome activation.
- CRM1 directly binds ASC's PYD domain, mediating its nuclear export.
- CRM1 inhibition attenuated EAE pathological symptoms in mice.
Conclusions:
- CRM1 is essential for ASC nuclear export, promoting inflammasome assembly and activation.
- CRM1 represents a potential therapeutic target for inflammasome-mediated inflammatory diseases.
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