Mechanistic insight into the attenuation of gouty inflammation by Taiwanese green propolis via inhibition of the NLRP3 inflammasome.

Abstract

Dysregulation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including gouty arthritis. Activation of the NLRP3 inflammasome requires priming and activation signals: the priming signal controls the expression of NLRP3 and interleukin (IL)-1β precursor (proIL-1β), while the activation signal leads to the assembly of the NLRP3 inflammasome and to caspase-1 activation. Here, we reported the effects of the alcoholic extract of Taiwanese green propolis (TGP) on the NLRP3 inflammasome in vitro and in vivo. TGP inhibited proIL-1β expression by reducing nuclear factor kappa B activation and reactive oxygen species (ROS) production in lipopolysaccharide-activated macrophages. Additionally, TGP also suppressed the activation signal by reducing mitochondrial damage, ROS production, lysosomal rupture, c-Jun N-terminal kinases 1/2 phosphorylation and apoptosis-associated speck-like protein oligomerization. Furthermore, we found that TGP inhibited the NLRP3 inflammasome partially via autophagy induction. In the in vivo mouse model of uric acid crystal-induced peritonitis, TGP attenuated the peritoneal recruitment of neutrophils, and the levels of IL-1β, active caspase-1, IL-6 and monocyte chemoattractant protein-1 in lavage fluids. As a proof of principle, in this study, we purified a known compound, propolin G, from TGP and identified this compound as a potential inhibitor of the NLRP3 inflammasome. Our results indicated that TGP might be useful for ameliorating gouty inflammation via inhibition of the NLRP3 inflammasome.

• Authors: Chih-Yu Hsieh, Lan-Hui Li, Yerra Koteswara Rao, Tz-Chuen Ju, Yu-Shin Nai, Yue-Wen Chen, Kuo-Feng Hua
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 4 Pg. 4081-4094 (04 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30370562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Nlrp3 protein, mouse
• Propolis

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Arthritis, Gouty (immunology, metabolism, prevention & control)
• Autophagy (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Humans
• Inflammation Mediators (metabolism)
• Macrophages (drug effects, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Peritonitis (immunology, metabolism, prevention & control)
• Propolis (pharmacology)
• Signal Transduction
• THP-1 Cells