The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic ShockReportar como inadecuado




The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Mediators of Inflammation - Volume 2017 2017, Article ID 6543237, 11 pages - https:-doi.org-10.1155-2017-6543237

Research ArticleMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Correspondence should be addressed to Xin Liu and Jiang Zheng

Received 12 September 2016; Revised 19 January 2017; Accepted 30 January 2017; Published 22 February 2017

Academic Editor: Hermann Gram

Copyright © 2017 Xiaoli Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of the NLRP3 inflammasome, which catalyzes maturation of proinflammatory cytokines like IL-1β and IL-18, is implicated and essentially involved in many kinds of inflammatory disorders. Chloroquine CQ is a traditional antimalarial drug and also possesses an anti-inflammatory property. In this study, we investigated whether CQ suppresses NLRP3 inflammasome activation and thereby confers protection against murine endotoxic shock. CQ attenuated NF-κB and MAPK activation and prohibited expression of IL-1β, IL-18, and Nlrp3 in LPS treated murine bone marrow-derived macrophages BMDMs, demonstrating its inhibitory effect on the priming signal of NLRP3 activation. Then, CQ was shown to inhibit caspase-1 activation and ASC specks formation in BMDMs, which indicates that CQ also suppresses inflammasome assembly, the second signal for NLRP3 inflammasome activation. In a murine endotoxic shock model, CQ effectively improved survival and markedly reduced IL-1β and IL-18 production in serum, peritoneal fluid, and lung tissues. Moreover, CQ reduced protein levels of NLRP3 and caspases-1 p10 in lung homogenates of mice with endotoxic shock, which may possibly explain its anti-inflammatory activity and life protection efficacy in vivo. Overall, our results demonstrate a new role of CQ that facilitates negative regulation on NLRP3 inflammasome, which thereby confers protection against lethal endotoxic shock.





Autor: Xiaoli Chen, Ning Wang, Yuanfeng Zhu, Yongling Lu, Xin Liu, and Jiang Zheng

Fuente: https://www.hindawi.com/



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