PMID- 28321151
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20181113
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2017
DP  - 2017
TI  - The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation 
      and Confers Protection against Murine Endotoxic Shock.
PG  - 6543237
LID - 10.1155/2017/6543237 [doi]
LID - 6543237
AB  - Activation of the NLRP3 inflammasome, which catalyzes maturation of 
      proinflammatory cytokines like IL-1beta 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-kappaB and MAPK activation and prohibited expression of IL-1beta, 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-1beta 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.
FAU - Chen, Xiaoli
AU  - Chen X
AUID- ORCID: 0000-0003-3513-3551
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
FAU - Wang, Ning
AU  - Wang N
AUID- ORCID: 0000-0002-9913-5006
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
FAU - Zhu, Yuanfeng
AU  - Zhu Y
AUID- ORCID: 0000-0002-6414-6709
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
FAU - Lu, Yongling
AU  - Lu Y
AUID- ORCID: 0000-0003-0092-7036
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
FAU - Liu, Xin
AU  - Liu X
AUID- ORCID: 0000-0002-2986-6364
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
FAU - Zheng, Jiang
AU  - Zheng J
AUID- ORCID: 0000-0002-9049-2234
AD  - Medical Research Center, Southwest Hospital, Third Military Medical University, 
      Chongqing 400038, China.
LA  - eng
PT  - Journal Article
DEP - 20170222
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antimalarials)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antimalarials/*therapeutic use
MH  - Chloroquine/*therapeutic use
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Inflammasomes/drug effects/*metabolism
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Signal Transduction/drug effects
PMC - PMC5340938
COIS- The authors declare that there are no competing interests regarding the 
      publication of this paper.
EDAT- 2017/03/23 06:00
MHDA- 2017/06/06 06:00
PMCR- 2017/02/22
CRDT- 2017/03/22 06:00
PHST- 2016/09/12 00:00 [received]
PHST- 2017/01/19 00:00 [revised]
PHST- 2017/01/30 00:00 [accepted]
PHST- 2017/03/22 06:00 [entrez]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2017/02/22 00:00 [pmc-release]
AID - 10.1155/2017/6543237 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2017;2017:6543237. doi: 10.1155/2017/6543237. Epub 2017 Feb 
      22.