A schematic diagram reveals ICA-mediated NLRP3 K593ca limits NLRP3-driven irritation. Credit score: Li Xinjian’s group
In a current research revealed in Science Advances, researchers led by Prof. Li Xinjian from the Institute of Biophysics of the Chinese language Academy of Sciences have uncovered a novel immunoregulatory operate of isocyanic acid (ICA), a reactive metabolite synthesized by the enzyme laccase area containing 1 (LACC1).
The researchers discovered that ICA performs a vital function in limiting irritation by disrupting NLRP3 inflammasome activation in macrophages. The invention gives new insights into the metabolic regulation of inflammatory responses and potential therapeutic targets for inflammatory illnesses.
LACC1, a metabolic enzyme extremely expressed in inflammatory macrophages, has lengthy been acknowledged for its function in breaking down citrulline into ornithine and ICA. Whereas earlier research have related ICA-induced protein carbamoylation with numerous illnesses, its function in immune regulation remained unclear.
The research demonstrates that lipopolysaccharide (LPS) stimulation triggers LACC1-dependent ICA manufacturing, which subsequently modifies NLRP3 and impairs inflammasome formation at lysine-593, disrupting its interplay with NEK7, a vital step in inflammasome activation. The inhibition of NLRP3 activation in the end ends in an attenuated inflammatory response.
This post-translational modification disrupts the formation of the inflammasome advanced, thereby lowering irritation. Lack of ICA manufacturing, both by means of LACC1 knockout or mutation of lysine-593 in NLRP3, led to an exaggerated inflammatory response in each in vitro and in vivo fashions.
The findings recommend that ICA acts as a pure inhibitor of NLRP3 inflammasome activation. This discovery opens new avenues for therapeutic interventions focusing on inflammasome-driven illnesses. Modulating ICA ranges or mimicking its results may present novel methods for treating inflammatory situations linked to NLRP3 dysregulation.
Extra info:
Zhenxing Zhang et al, Isocyanic acid–mediated NLRP3 carbamoylation reduces NLRP3-NEK7 interplay and limits inflammasome activation, Science Advances (2025). DOI: 10.1126/sciadv.adq4266
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Chinese language Academy of Sciences
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Isocyanic acid recognized as anti-inflammatory metabolite (2025, March 13)
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