Management of Gout-associated MSU crystals-induced NLRP3 inflammasome activation by procyanidin B2: targeting IL-1β and Cathepsin B in macrophages.

Abstract

Gout, the most prevalent inflammatory arthritis worldwide, released interleukin-1β (IL-1β) and Cathepsin B inflammatory mediators that constitute the hallmark of the disease. Herein we aimed to investigate whether procyanidin B2 (PCB2), a natural dietary compound, can suppress MSU crystals-stimulated gouty inflammation. Treated with lipopolysaccharide (LPS) plus MSU, both mouse peritoneal macrophages (MPM) and mouse bone marrow-derived macrophages (BMDM) released a large amount of mature IL-1β compared to those treated with MSU or LPS alone, while IL-1β release was blocked by TLR4 and its downstream effector inhibitors. In two mouse models of gout, oral administration of PCB2 suppressed MSU crystals-induced increasing expression of IL-1β, Cathepsin B and NLRP3 in the air pouch skin and paws, accompanied with the downregulation prostaglandin E2 (PGE2) in pouch exudates. Inflammatory immune cell infiltration including macrophages and neutrophils were significantly blocked by PCB2 in air pouch skin and paws of mice gout groups. PCB2 also suppressed the release of IL-1β and Cathepsin B induced by MSU plus LPS in MPM. Our results suggest that the inhibitory effects of PCB2 on NLRP3 inflammasome may alleviate inflammatory response in gout, and this might be a promising anti-inflammatory mechanism of PCB2 against the inflammation in gout.

• Authors: Chun-Ying Qiao, Ying Li, Yue Shang, Min Jiang, Jian Liu, Zi-Ying Zhan, Huan Ye, Yong-Ce Lin, Jing-Ya Jiao, Rong-Hui Sun, Zhi-Hong Zhang, Mei-Hua Piao, Yan-Ling Wu, Ji-Xing Nan, Li-Hua Lian
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 28 Issue 6 Pg. 1481-1493 (Dec 2020) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 33006110 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Biflavonoids
• Cytokines
• IL1B protein, mouse
• Inflammasomes
• Interleukin-1beta
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Proanthocyanidins
• Uric Acid
• procyanidin B2
• Catechin
• Cathepsin B
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Biflavonoids (pharmacology)
• Catechin (pharmacology)
• Cathepsin B (metabolism)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Gout (drug therapy, metabolism)
• Inflammasomes (drug effects, metabolism)
• Inflammation (drug therapy, metabolism)
• Interleukin-1beta (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neutrophils (drug effects, metabolism)
• Proanthocyanidins (pharmacology)
• Uric Acid (metabolism)