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Published in: Inflammopharmacology 6/2020

01-12-2020 | Colchicine | Original Article

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

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

Published in: Inflammopharmacology | Issue 6/2020

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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.
Literature
go back to reference Amaral EP et al (2018) Lysosomal cathepsin release is required for NLRP3-inflammasome activation by Mycobacterium tuberculosis in infected macrophages. Front Immunol 9:1427CrossRef Amaral EP et al (2018) Lysosomal cathepsin release is required for NLRP3-inflammasome activation by Mycobacterium tuberculosis in infected macrophages. Front Immunol 9:1427CrossRef
go back to reference Zurek M (2006) Pathogenesis, diagnostics and therapy of gout. Vnitr Lek 52:736–741PubMed Zurek M (2006) Pathogenesis, diagnostics and therapy of gout. Vnitr Lek 52:736–741PubMed
Metadata
Title
Management of Gout-associated MSU crystals-induced NLRP3 inflammasome activation by procyanidin B2: targeting IL-1β and Cathepsin B in macrophages
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
Publication date
01-12-2020
Publisher
Springer International Publishing
Keywords
Colchicine
Gout
Published in
Inflammopharmacology / Issue 6/2020
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-020-00758-8

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