Corticosteroids alleviate lipopolysaccharide‐induced inflammation and lung injury via inhibiting NLRP3‐inflammasome activation
The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)‐induced inflammation and ALI. We used corticosteroid treatment for LPS‐induced murine ALI model to investigate the...
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| description | The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)‐induced inflammation and ALI. We used corticosteroid treatment for LPS‐induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS‐stimulated macrophages were used to explore the specific anti‐inflammatory effects of corticosteroids on NLRP3‐inflammasome in vitro. We found corticosteroids attenuated LPS‐induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) in Lung. In vitro, when NLRP3‐inflammasome was knocked out, inflammatory response of caspase‐1 activation and IL‐1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase‐1 and the maturation of IL‐1β, which depended on inhibiting the nuclear factor‐κB (NF‐κB) signal pathway activation. However, when corticosteroids intervened the LPS‐primed macrophages, it also negatively regulated NLRP3‐inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS‐induced inflammation and ALI by suppressing both NF‐κB signal pathway and mtROS‐dependent NLRP3 inflammasome activation. |
| doi_str_mv | 10.1111/jcmm.15849 |
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This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)‐induced inflammation and ALI. We used corticosteroid treatment for LPS‐induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS‐stimulated macrophages were used to explore the specific anti‐inflammatory effects of corticosteroids on NLRP3‐inflammasome in vitro. We found corticosteroids attenuated LPS‐induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) in Lung. In vitro, when NLRP3‐inflammasome was knocked out, inflammatory response of caspase‐1 activation and IL‐1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase‐1 and the maturation of IL‐1β, which depended on inhibiting the nuclear factor‐κB (NF‐κB) signal pathway activation. However, when corticosteroids intervened the LPS‐primed macrophages, it also negatively regulated NLRP3‐inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS‐induced inflammation and ALI by suppressing both NF‐κB signal pathway and mtROS‐dependent NLRP3 inflammasome activation.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.15849</identifier><identifier>PMID: 32977368</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Acute Lung Injury ; Adrenal Cortex Hormones - pharmacology ; Adrenal Cortex Hormones - therapeutic use ; Alveoli ; Animals ; Caspase ; Caspase 1 - metabolism ; Corticosteroids ; Cytokines ; Dexamethasone - pharmacology ; Dexamethasone - therapeutic use ; Enzyme Activation - drug effects ; Experiments ; Flow cytometry ; Inflammasomes ; Inflammasomes - antagonists & inhibitors ; Inflammasomes - metabolism ; Inflammation ; Inflammation - chemically induced ; Inflammation - drug therapy ; Inflammation - metabolism ; Interleukin-18 - metabolism ; Leukocytes (neutrophilic) ; Lipopolysaccharides ; Lungs ; Macrophages ; Mice, Inbred C57BL ; Microscopy ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; mitochondrial reactive oxygen species ; Models, Biological ; Neutrophils ; NF-kappa B - metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; NLRP3‐inflammasome ; Original ; Pathogens ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Signal Transduction ; Software</subject><ispartof>Journal of cellular and molecular medicine, 2020-11, Vol.24 (21), p.12716-12725</ispartof><rights>2020 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd</rights><rights>2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4489-b569cd0a3d9013516a5a052c76fa5d241b0ed4a02894dcf7b0765c933692991a3</citedby><cites>FETCH-LOGICAL-c4489-b569cd0a3d9013516a5a052c76fa5d241b0ed4a02894dcf7b0765c933692991a3</cites><orcidid>0000-0002-8039-8973</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686976/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686976/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32977368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Jia‐Wei</creatorcontrib><creatorcontrib>Mao, Bei</creatorcontrib><creatorcontrib>Tao, Ru‐Jia</creatorcontrib><creatorcontrib>Fan, Li‐Chao</creatorcontrib><creatorcontrib>Lu, Hai‐Wen</creatorcontrib><creatorcontrib>Ge, Bao‐Xue</creatorcontrib><creatorcontrib>Xu, Jin‐Fu</creatorcontrib><title>Corticosteroids alleviate lipopolysaccharide‐induced inflammation and lung injury via inhibiting NLRP3‐inflammasome activation</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)‐induced inflammation and ALI. We used corticosteroid treatment for LPS‐induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS‐stimulated macrophages were used to explore the specific anti‐inflammatory effects of corticosteroids on NLRP3‐inflammasome in vitro. We found corticosteroids attenuated LPS‐induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) in Lung. In vitro, when NLRP3‐inflammasome was knocked out, inflammatory response of caspase‐1 activation and IL‐1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase‐1 and the maturation of IL‐1β, which depended on inhibiting the nuclear factor‐κB (NF‐κB) signal pathway activation. However, when corticosteroids intervened the LPS‐primed macrophages, it also negatively regulated NLRP3‐inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS‐induced inflammation and ALI by suppressing both NF‐κB signal pathway and mtROS‐dependent NLRP3 inflammasome activation.</description><subject>Acute Lung Injury</subject><subject>Adrenal Cortex Hormones - pharmacology</subject><subject>Adrenal Cortex Hormones - therapeutic use</subject><subject>Alveoli</subject><subject>Animals</subject><subject>Caspase</subject><subject>Caspase 1 - metabolism</subject><subject>Corticosteroids</subject><subject>Cytokines</subject><subject>Dexamethasone - pharmacology</subject><subject>Dexamethasone - therapeutic use</subject><subject>Enzyme Activation - drug effects</subject><subject>Experiments</subject><subject>Flow cytometry</subject><subject>Inflammasomes</subject><subject>Inflammasomes - antagonists & inhibitors</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Interleukin-18 - metabolism</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipopolysaccharides</subject><subject>Lungs</subject><subject>Macrophages</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>mitochondrial reactive oxygen species</subject><subject>Models, Biological</subject><subject>Neutrophils</subject><subject>NF-kappa B - metabolism</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>NLRP3‐inflammasome</subject><subject>Original</subject><subject>Pathogens</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Signal Transduction</subject><subject>Software</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc-KFDEQxoMo7rp68QGkwYsIsyaddNK5CDL4l1kV0XOoTtI7GdLJbNI9MjfxCXxGn8Ts9LioB3OpovL7Pqr4EHpI8Dkp79lGD8M5aVomb6HTUusFk5TdPvakpe0JupfzBmPKCZV30QmtpRCUt6fo-zKm0emYR5uiM7kC7-3OwWgr77ZxG_0-g9ZrSM7Yn99-uGAmbU3lQu9hGGB0MVQQTOWncFmmmyntq6Iv7dp1bnRl-n716SM9aGdNjoOtQI9ud5DfR3d68Nk-ONYz9OXVy8_LN4vVh9dvly9WC81YKxddw6U2GKiRmNCGcGgAN7UWvIfG1Ix02BoGuG4lM7oXHRa80ZJSLmspCdAz9Hz23U7dYI22YUzg1Ta5AdJeRXDq75_g1uoy7pTgLZeCF4MnR4MUryabRzW4rK33EGycsqoZ41xg1tKCPv4H3cQphXJeoTiVJQjRFOrpTOkUc062v1mGYHUdrbqOVh2iLfCjP9e_QX9nWQAyA1-dt_v_WKl3y4uL2fQX3WO0YA</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Yang, Jia‐Wei</creator><creator>Mao, Bei</creator><creator>Tao, Ru‐Jia</creator><creator>Fan, Li‐Chao</creator><creator>Lu, Hai‐Wen</creator><creator>Ge, Bao‐Xue</creator><creator>Xu, Jin‐Fu</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8039-8973</orcidid></search><sort><creationdate>202011</creationdate><title>Corticosteroids alleviate lipopolysaccharide‐induced inflammation and lung injury via inhibiting NLRP3‐inflammasome activation</title><author>Yang, Jia‐Wei ; Mao, Bei ; Tao, Ru‐Jia ; Fan, Li‐Chao ; Lu, Hai‐Wen ; Ge, Bao‐Xue ; Xu, Jin‐Fu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4489-b569cd0a3d9013516a5a052c76fa5d241b0ed4a02894dcf7b0765c933692991a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute Lung Injury</topic><topic>Adrenal Cortex Hormones - pharmacology</topic><topic>Adrenal Cortex Hormones - therapeutic use</topic><topic>Alveoli</topic><topic>Animals</topic><topic>Caspase</topic><topic>Caspase 1 - metabolism</topic><topic>Corticosteroids</topic><topic>Cytokines</topic><topic>Dexamethasone - pharmacology</topic><topic>Dexamethasone - therapeutic use</topic><topic>Enzyme Activation - drug effects</topic><topic>Experiments</topic><topic>Flow cytometry</topic><topic>Inflammasomes</topic><topic>Inflammasomes - antagonists & inhibitors</topic><topic>Inflammasomes - metabolism</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Interleukin-18 - metabolism</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lipopolysaccharides</topic><topic>Lungs</topic><topic>Macrophages</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>mitochondrial reactive oxygen species</topic><topic>Models, Biological</topic><topic>Neutrophils</topic><topic>NF-kappa B - metabolism</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>NLRP3‐inflammasome</topic><topic>Original</topic><topic>Pathogens</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Signal Transduction</topic><topic>Software</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Jia‐Wei</creatorcontrib><creatorcontrib>Mao, Bei</creatorcontrib><creatorcontrib>Tao, Ru‐Jia</creatorcontrib><creatorcontrib>Fan, Li‐Chao</creatorcontrib><creatorcontrib>Lu, Hai‐Wen</creatorcontrib><creatorcontrib>Ge, Bao‐Xue</creatorcontrib><creatorcontrib>Xu, Jin‐Fu</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Jia‐Wei</au><au>Mao, Bei</au><au>Tao, Ru‐Jia</au><au>Fan, Li‐Chao</au><au>Lu, Hai‐Wen</au><au>Ge, Bao‐Xue</au><au>Xu, Jin‐Fu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Corticosteroids alleviate lipopolysaccharide‐induced inflammation and lung injury via inhibiting NLRP3‐inflammasome activation</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2020-11</date><risdate>2020</risdate><volume>24</volume><issue>21</issue><spage>12716</spage><epage>12725</epage><pages>12716-12725</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)‐induced inflammation and ALI. We used corticosteroid treatment for LPS‐induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS‐stimulated macrophages were used to explore the specific anti‐inflammatory effects of corticosteroids on NLRP3‐inflammasome in vitro. We found corticosteroids attenuated LPS‐induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) in Lung. In vitro, when NLRP3‐inflammasome was knocked out, inflammatory response of caspase‐1 activation and IL‐1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase‐1 and the maturation of IL‐1β, which depended on inhibiting the nuclear factor‐κB (NF‐κB) signal pathway activation. However, when corticosteroids intervened the LPS‐primed macrophages, it also negatively regulated NLRP3‐inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS‐induced inflammation and ALI by suppressing both NF‐κB signal pathway and mtROS‐dependent NLRP3 inflammasome activation.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32977368</pmid><doi>10.1111/jcmm.15849</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8039-8973</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Lung Injury Adrenal Cortex Hormones - pharmacology Adrenal Cortex Hormones - therapeutic use Alveoli Animals Caspase Caspase 1 - metabolism Corticosteroids Cytokines Dexamethasone - pharmacology Dexamethasone - therapeutic use Enzyme Activation - drug effects Experiments Flow cytometry Inflammasomes Inflammasomes - antagonists & inhibitors Inflammasomes - metabolism Inflammation Inflammation - chemically induced Inflammation - drug therapy Inflammation - metabolism Interleukin-18 - metabolism Leukocytes (neutrophilic) Lipopolysaccharides Lungs Macrophages Mice, Inbred C57BL Microscopy Mitochondria Mitochondria - drug effects Mitochondria - metabolism mitochondrial reactive oxygen species Models, Biological Neutrophils NF-kappa B - metabolism NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors NLR Family, Pyrin Domain-Containing 3 Protein - metabolism NLRP3‐inflammasome Original Pathogens Proteins Reactive oxygen species Reactive Oxygen Species - metabolism Signal Transduction Software |
| title | Corticosteroids alleviate lipopolysaccharide‐induced inflammation and lung injury via inhibiting NLRP3‐inflammasome activation |
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