Caffeine Inhibits NLRP3 Inflammasome Activation by Suppressing MAPK/NF-κB and A2aR Signaling in LPS-Induced THP-1 Macrophages
Identifieur interne : 000976 ( Main/Exploration ); précédent : 000975; suivant : 000977Caffeine Inhibits NLRP3 Inflammasome Activation by Suppressing MAPK/NF-κB and A2aR Signaling in LPS-Induced THP-1 Macrophages
Auteurs : Weiming Zhao ; Li Ma ; Cheng Cai ; Xiaohui GongSource :
- International Journal of Biological Sciences [ 1449-2288 ] ; 2019.
Abstract
Excessive inflammation induced by various risk factors is associated with the development of bronchopulmonary dysplasia (BPD). Caffeine exerts potent anti-inflammatory effects as a clinical preventive medicine for BPD. Recently, NLRP3 inflammasome activation has been demonstrated to be essential for the pathogenesis of BPD. In the present study, we aimed to investigate the effects of caffeine on NLRP3 inflammasome activation in LPS-induced THP-1 macrophages and to explore the underlying the detailed mechanism. We found that caffeine significantly reduced NLRP3 expression, ASC speck formation, and caspase 1 cleavage and therefore decreased IL-1β and IL-18 secretion in THP-1 macrophages. Caffeine also markedly decreased the phosphorylation levels of MAPK and NF-κB pathway members, further suppressing the translocation of NF-κB in THP-1 macrophages. Moreover, silencing of the caffeine-antagonized adenosine A2a receptor (A2aR) significantly decreased cleaved caspase 1 expression in THP-1 macrophages by reducing ROS production. Given these findings, we conclude that caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-κB signaling and A2aR-associated ROS production in LPS-induced THP-1 macrophages.
Url:
DOI: 10.7150/ijbs.34211
PubMed: 31360100
PubMed Central: 6643212
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Caffeine Inhibits NLRP3 Inflammasome Activation by Suppressing MAPK/NF-κB and A2aR Signaling in LPS-Induced THP-1 Macrophages</title><author><name sortKey="Zhao, Weiming" sort="Zhao, Weiming" uniqKey="Zhao W" first="Weiming" last="Zhao">Weiming Zhao</name></author><author><name sortKey="Ma, Li" sort="Ma, Li" uniqKey="Ma L" first="Li" last="Ma">Li Ma</name></author><author><name sortKey="Cai, Cheng" sort="Cai, Cheng" uniqKey="Cai C" first="Cheng" last="Cai">Cheng Cai</name></author><author><name sortKey="Gong, Xiaohui" sort="Gong, Xiaohui" uniqKey="Gong X" first="Xiaohui" last="Gong">Xiaohui Gong</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31360100</idno><idno type="pmc">6643212</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643212</idno><idno type="RBID">PMC:6643212</idno><idno type="doi">10.7150/ijbs.34211</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000593</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000593</idno><idno type="wicri:Area/Pmc/Curation">000593</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000593</idno><idno type="wicri:Area/Pmc/Checkpoint">000912</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000912</idno><idno type="wicri:Area/Ncbi/Merge">000857</idno><idno type="wicri:Area/Ncbi/Curation">000857</idno><idno type="wicri:Area/Ncbi/Checkpoint">000857</idno><idno type="wicri:Area/Main/Merge">000976</idno><idno type="wicri:Area/Main/Curation">000976</idno><idno type="wicri:Area/Main/Exploration">000976</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Caffeine Inhibits NLRP3 Inflammasome Activation by Suppressing MAPK/NF-κB and A2aR Signaling in LPS-Induced THP-1 Macrophages</title><author><name sortKey="Zhao, Weiming" sort="Zhao, Weiming" uniqKey="Zhao W" first="Weiming" last="Zhao">Weiming Zhao</name></author><author><name sortKey="Ma, Li" sort="Ma, Li" uniqKey="Ma L" first="Li" last="Ma">Li Ma</name></author><author><name sortKey="Cai, Cheng" sort="Cai, Cheng" uniqKey="Cai C" first="Cheng" last="Cai">Cheng Cai</name></author><author><name sortKey="Gong, Xiaohui" sort="Gong, Xiaohui" uniqKey="Gong X" first="Xiaohui" last="Gong">Xiaohui Gong</name></author></analytic><series><title level="j">International Journal of Biological Sciences</title><idno type="eISSN">1449-2288</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Excessive inflammation induced by various risk factors is associated with the development of bronchopulmonary dysplasia (BPD). Caffeine exerts potent anti-inflammatory effects as a clinical preventive medicine for BPD. Recently, NLRP3 inflammasome activation has been demonstrated to be essential for the pathogenesis of BPD. In the present study, we aimed to investigate the effects of caffeine on NLRP3 inflammasome activation in LPS-induced THP-1 macrophages and to explore the underlying the detailed mechanism. We found that caffeine significantly reduced NLRP3 expression, ASC speck formation, and caspase 1 cleavage and therefore decreased IL-1β and IL-18 secretion in THP-1 macrophages. Caffeine also markedly decreased the phosphorylation levels of MAPK and NF-κB pathway members, further suppressing the translocation of NF-κB in THP-1 macrophages. Moreover, silencing of the caffeine-antagonized adenosine A2a receptor (A2aR) significantly decreased cleaved caspase 1 expression in THP-1 macrophages by reducing ROS production. Given these findings, we conclude that caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-κB signaling and A2aR-associated ROS production in LPS-induced THP-1 macrophages.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Steinhorn, R" uniqKey="Steinhorn R">R Steinhorn</name></author><author><name sortKey="Davis, Jm" uniqKey="Davis J">JM Davis</name></author><author><name sortKey="Gopel, W" uniqKey="Gopel W">W Göpel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Owen, Ls" uniqKey="Owen L">LS Owen</name></author><author><name sortKey="Manley, Bj" uniqKey="Manley B">BJ Manley</name></author><author><name sortKey="Davis, Pg" uniqKey="Davis P">PG Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matta, P" uniqKey="Matta P">P Matta</name></author><author><name sortKey="Sherrod, Sd" uniqKey="Sherrod S">SD Sherrod</name></author><author><name 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