Related Experiment Video
Updated: May 14, 2026
09:04
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
CRY-NLRP3 complexes define a circadian checkpoint controlling inflammasome activation
Biorxiv : the Preprint Server for Biology
|May 13, 2026
Summary
Circadian clocks regulate rapid inflammatory responses by linking core clock proteins CRY1/CRY2 to the NLRP3 inflammasome. This CRY-NLRP3 complex acts as a checkpoint, influencing inflammation and drug response timing.
Area of Science:
- Immunology
- Chronobiology
- Molecular Biology
Background:
- Innate immune sensors like the NLRP3 inflammasome initiate rapid inflammatory responses.
- The influence of circadian clocks on these rapid immune decisions remains largely unexplored.
Purpose of the Study:
- To identify a circadian mechanism regulating NLRP3 inflammasome activation.
- To investigate the role of core clock components in modulating rapid inflammatory responses.
Main Methods:
- Protein association studies to identify interactions between NLRP3 and circadian proteins.
- Pharmacological manipulation of CRY protein stability in human macrophages.
- Assessment of inflammasome activation, IL-1β secretion, and pyroptosis.
- Analysis of circadian time-dependent inflammasome activation and drug response.
- Evaluation of NLRP3 variants associated with Cryopyrin-Associated Periodic Syndromes (CAPS).
Main Results:
- NLRP3 forms oscillatory complexes with circadian repressors CRY1 and CRY2, acting as a checkpoint.
- Stabilizing CRY proteins attenuates inflammasome activation, IL-1β secretion, and pyroptosis.
- NLRP3 inflammasome activation and its inhibition by MCC950 exhibit circadian rhythmicity.
- Specific NLRP3 variants linked to CAPS weaken CRY binding and alter time-of-day inflammasome patterns.
Conclusions:
- CRY-NLRP3 complexes represent a crucial circadian checkpoint modulating inflammasome activity.
- Circadian time critically influences NLRP3-driven inflammation and the response to NLRP3 inhibitors.
- Understanding this link has implications for treating inflammatory diseases and optimizing drug efficacy.
Related Concept Videos
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...