The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock.
Identifieur interne : 000C91 ( Main/Exploration ); précédent : 000C90; suivant : 000C92The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock.
Auteurs : Xiaoli Chen [République populaire de Chine] ; Ning Wang [République populaire de Chine] ; Yuanfeng Zhu [République populaire de Chine] ; Yongling Lu [République populaire de Chine] ; Xin Liu [République populaire de Chine] ; Jiang Zheng [République populaire de Chine]Source :
- Mediators of inflammation [ 1466-1861 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Anti-inflammatoires (usage thérapeutique), Antipaludiques (usage thérapeutique), Chloroquine (usage thérapeutique), Inflammasomes (), Inflammasomes (métabolisme), Interleukine-1 bêta (métabolisme), Interleukine-18 (métabolisme), Lipopolysaccharides (pharmacologie), Macrophages (), Macrophages (métabolisme), Mâle, Protéine-3 de la famille des NLR contenant un domaine pyrine (métabolisme), Souris, Souris de lignée BALB C, Test ELISA, Transduction du signal ().
- MESH :
- métabolisme : Inflammasomes, Interleukine-1 bêta, Interleukine-18, Macrophages, Protéine-3 de la famille des NLR contenant un domaine pyrine.
- pharmacologie : Lipopolysaccharides.
- usage thérapeutique : Anti-inflammatoires, Antipaludiques, Chloroquine.
- Animaux, Inflammasomes, Macrophages, Mâle, Souris, Souris de lignée BALB C, Test ELISA, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Anti-Inflammatory Agents (therapeutic use), Antimalarials (therapeutic use), Chloroquine (therapeutic use), Enzyme-Linked Immunosorbent Assay, Inflammasomes (drug effects), Inflammasomes (metabolism), Interleukin-18 (metabolism), Interleukin-1beta (metabolism), Lipopolysaccharides (pharmacology), Macrophages (drug effects), Macrophages (metabolism), Male, Mice, Mice, Inbred BALB C, NLR Family, Pyrin Domain-Containing 3 Protein (metabolism), Signal Transduction (drug effects).
- MESH :
- chemical , drug effects : Inflammasomes.
- chemical , metabolism : Inflammasomes, Interleukin-18, Interleukin-1beta, NLR Family, Pyrin Domain-Containing 3 Protein.
- chemical , pharmacology : Lipopolysaccharides.
- chemical , therapeutic use : Anti-Inflammatory Agents, Antimalarials, Chloroquine.
- drug effects : Macrophages, Signal Transduction.
- metabolism : Macrophages.
- Animals, Enzyme-Linked Immunosorbent Assay, Male, Mice, Mice, Inbred BALB C.
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.
DOI: 10.1155/2017/6543237
PubMed: 28321151
Affiliations:
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xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Ning" sort="Wang, Ning" uniqKey="Wang N" first="Ning" last="Wang">Ning Wang</name><affiliation wicri:level="1"><nlm:affiliation>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Yuanfeng" sort="Zhu, Yuanfeng" uniqKey="Zhu Y" first="Yuanfeng" last="Zhu">Yuanfeng Zhu</name><affiliation wicri:level="1"><nlm:affiliation>Medical Research Center, 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last="Liu">Xin Liu</name><affiliation wicri:level="1"><nlm:affiliation>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Jiang" sort="Zheng, Jiang" uniqKey="Zheng J" first="Jiang" last="Zheng">Jiang Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author></analytic><series><title level="j">Mediators of inflammation</title><idno type="eISSN">1466-1861</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Anti-Inflammatory Agents (therapeutic use)</term><term>Antimalarials (therapeutic use)</term><term>Chloroquine (therapeutic use)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Inflammasomes (drug effects)</term><term>Inflammasomes (metabolism)</term><term>Interleukin-18 (metabolism)</term><term>Interleukin-1beta (metabolism)</term><term>Lipopolysaccharides (pharmacology)</term><term>Macrophages (drug effects)</term><term>Macrophages (metabolism)</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)</term><term>Signal Transduction (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anti-inflammatoires (usage thérapeutique)</term><term>Antipaludiques (usage thérapeutique)</term><term>Chloroquine (usage thérapeutique)</term><term>Inflammasomes ()</term><term>Inflammasomes (métabolisme)</term><term>Interleukine-1 bêta (métabolisme)</term><term>Interleukine-18 (métabolisme)</term><term>Lipopolysaccharides (pharmacologie)</term><term>Macrophages ()</term><term>Macrophages (métabolisme)</term><term>Mâle</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Test ELISA</term><term>Transduction du signal ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Inflammasomes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Inflammasomes</term><term>Interleukin-18</term><term>Interleukin-1beta</term><term>NLR Family, Pyrin Domain-Containing 3 Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Inflammatory Agents</term><term>Antimalarials</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Macrophages</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Inflammasomes</term><term>Interleukine-1 bêta</term><term>Interleukine-18</term><term>Macrophages</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anti-inflammatoires</term><term>Antipaludiques</term><term>Chloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Inflammasomes</term><term>Macrophages</term><term>Mâle</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Test ELISA</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Activation of the NLRP3 inflammasome, which catalyzes maturation of proinflammatory cytokines like IL-1<i>β</i> 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-<i>κ</i>B and MAPK activation and prohibited expression of IL-1<i>β</i>, IL-18, and <i>Nlrp3</i> 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-1<i>β</i> 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.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen, Xiaoli" sort="Chen, Xiaoli" uniqKey="Chen X" first="Xiaoli" last="Chen">Xiaoli Chen</name></noRegion><name sortKey="Liu, Xin" sort="Liu, Xin" uniqKey="Liu X" first="Xin" last="Liu">Xin Liu</name><name sortKey="Lu, Yongling" sort="Lu, Yongling" uniqKey="Lu Y" first="Yongling" last="Lu">Yongling Lu</name><name sortKey="Wang, Ning" sort="Wang, Ning" uniqKey="Wang N" first="Ning" last="Wang">Ning Wang</name><name sortKey="Zheng, Jiang" sort="Zheng, Jiang" uniqKey="Zheng J" first="Jiang" last="Zheng">Jiang Zheng</name><name sortKey="Zhu, Yuanfeng" sort="Zhu, Yuanfeng" uniqKey="Zhu Y" first="Yuanfeng" last="Zhu">Yuanfeng Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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