Curcumin analogue AI-44 alleviates MSU-induced gouty arthritis in mice via inhibiting cathepsin B-mediated NLRP3 inflammasome activation.

Abstract

NOD-like receptors (NLRs), as a part of intracellular pattern recognition receptors (PRR), are important regulators in innate immune system. The NLRP3 inflammasome which is a member of NLRs has been linked to several human inflammatory diseases. Gouty arthritis is triggered when the deposition of monosodium urate (MSU) crystals in joints induces acute inflammation characterized by the recruitment of macrophages and neutrophils. In this study, we explored the curcumin analogue AI-44 alleviated the gouty arthritis in mice via suppressing MSU engaging NLRP3 inflammasome activation. Furthermore, we demonstrated that AI-44 inhibited the interaction of cathepsin B and NLRP3 to prevent the activation of NLRP3 inflammasome. Moreover, we found AI-44 inhibited the enzyme activity of cathepsin B and bound to the key residue E122 in cytoplasm but not in lysosome. Collectively, these data suggest that AI-44 is a novel drug candidate for the treatment of gouty arthritis through targeting cathepsin B and inhibiting NLRP3 inflammasome activation.

• Authors: Yanpin Gu, Yongcheng Zhu, Guoliang Deng, Songjun Liu, Yang Sun, Wen Lv
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 93 Pg. 107375 (Apr 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 33517224 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Uric Acid
• Cathepsin B
• Curcumin

Topics

• Animals
• Arthritis, Gouty (chemically induced, drug therapy, immunology)
• Cathepsin B (immunology)
• Curcumin (analogs & derivatives, pharmacology, therapeutic use)
• Female
• Humans
• Inflammasomes (immunology)
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (immunology)
• THP-1 Cells
• Uric Acid
• Mice