CTRP4 acts as an anti‐inflammatory factor in macrophages and protects against endotoxic shock
Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS‐induced endotoxemia and cecal ligation a...
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| Veröffentlicht in: | European journal of immunology 2021-02, Vol.51 (2), p.380-392 |
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| creator | Cao, Lulu Tan, Weifeng Chen, Wei Huang, He He, Minwei Li, Qi Zhu, Xiaoxin Wang, Lu |
| description | Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS‐induced endotoxemia and cecal ligation and puncture (CLP)–induced sepsis, we investigated the effects of C1q/TNF‐related protein 4(CTRP4) on septic lethality and sepsis‐induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4‐expressing macrophages as the key cell type inhibiting LPS‐induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.
CTRP4 decreased the mortalities of mice and pathological lung injury in the endotoxic shock model. The molecular mechanism behind this phenomenon remains that CTRP4 inhibited TLR4 internalization and activated downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. |
| doi_str_mv | 10.1002/eji.202048617 |
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CTRP4 decreased the mortalities of mice and pathological lung injury in the endotoxic shock model. The molecular mechanism behind this phenomenon remains that CTRP4 inhibited TLR4 internalization and activated downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.202048617</identifier><identifier>PMID: 33080044</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adipokines - metabolism ; Adoptive transfer ; Animals ; Anti-Inflammatory Agents - metabolism ; Antibiotics ; Cecum ; Cells, Cultured ; Clinical trials ; CTRP4 ; Cytokine storm ; Cytokines ; Cytokines - metabolism ; Disease Models, Animal ; Endotoxemia ; Endotoxemia - chemically induced ; Endotoxemia - metabolism ; endotoxic ; Inflammation ; Inflammation - chemically induced ; Inflammation - metabolism ; Internalization ; Lethality ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; LPS ; Lung Injury - chemically induced ; Lung Injury - metabolism ; macrophage ; Macrophages ; Macrophages - metabolism ; Mice ; Mice, Inbred C57BL ; Sepsis ; Septic shock ; Shock, Septic - chemically induced ; Shock, Septic - metabolism ; TLR4 ; TLR4 protein ; Toll-like receptors ; Tumor necrosis factor</subject><ispartof>European journal of immunology, 2021-02, Vol.51 (2), p.380-392</ispartof><rights>2020 Wiley‐VCH GmbH</rights><rights>2020 Wiley-VCH GmbH.</rights><rights>2021 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4037-d5fdf651e10ef7f040819a447fbe4443ac7c3b3ea0ff96ce09467d95914325523</citedby><cites>FETCH-LOGICAL-c4037-d5fdf651e10ef7f040819a447fbe4443ac7c3b3ea0ff96ce09467d95914325523</cites><orcidid>0000-0003-0835-0198</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Feji.202048617$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.202048617$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,1432,27922,27923,45572,45573,46407,46831</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33080044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Lulu</creatorcontrib><creatorcontrib>Tan, Weifeng</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Huang, He</creatorcontrib><creatorcontrib>He, Minwei</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Zhu, Xiaoxin</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><title>CTRP4 acts as an anti‐inflammatory factor in macrophages and protects against endotoxic shock</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS‐induced endotoxemia and cecal ligation and puncture (CLP)–induced sepsis, we investigated the effects of C1q/TNF‐related protein 4(CTRP4) on septic lethality and sepsis‐induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4‐expressing macrophages as the key cell type inhibiting LPS‐induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.
CTRP4 decreased the mortalities of mice and pathological lung injury in the endotoxic shock model. The molecular mechanism behind this phenomenon remains that CTRP4 inhibited TLR4 internalization and activated downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm.</description><subject>Adipokines - metabolism</subject><subject>Adoptive transfer</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - metabolism</subject><subject>Antibiotics</subject><subject>Cecum</subject><subject>Cells, Cultured</subject><subject>Clinical trials</subject><subject>CTRP4</subject><subject>Cytokine storm</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Endotoxemia</subject><subject>Endotoxemia - chemically induced</subject><subject>Endotoxemia - metabolism</subject><subject>endotoxic</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Internalization</subject><subject>Lethality</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>LPS</subject><subject>Lung Injury - chemically induced</subject><subject>Lung Injury - metabolism</subject><subject>macrophage</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Sepsis</subject><subject>Septic shock</subject><subject>Shock, Septic - chemically induced</subject><subject>Shock, Septic - metabolism</subject><subject>TLR4</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>Tumor necrosis factor</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFPwjAYhhujEUSPXs0Sz8Ov7ddtPRqCiiHRGDw3ZWthyDZsR5SbP8Hf6C-xiHI0eZMe-vTt9z2EnFPoUwB2ZRZlnwEDzBKaHpAuFYzGSJEeki4AxZjJDDrkxPsFAMhEyGPS4RwyAMQuUYPJ0yNGOm99pEPqkLb8-vgsa7vUVaXbxm0iG-4bF5V1VOncNau5npktXEQr17Tm5_FMl7VvI1MXTdu8l3nk503-ckqOrF56c_Z79sjzzXAyuIvHD7ejwfU4zhF4GhfCFjYR1FAwNrWAkFGpEVM7NYjIdZ7mfMqNBmtlkhuQmKSFFJIiZ0Iw3iOXu94w0Ova-FYtmrWrw5eKBTUCIWE0UPGOCkt474xVK1dW2m0UBbXVqYJOtdcZ-Ivf1vW0MsWe_vMXALYD3sql2fzfpob3I5Qs5d-KUX_5</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Cao, Lulu</creator><creator>Tan, Weifeng</creator><creator>Chen, Wei</creator><creator>Huang, He</creator><creator>He, Minwei</creator><creator>Li, Qi</creator><creator>Zhu, Xiaoxin</creator><creator>Wang, Lu</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0003-0835-0198</orcidid></search><sort><creationdate>202102</creationdate><title>CTRP4 acts as an anti‐inflammatory factor in macrophages and protects against endotoxic shock</title><author>Cao, Lulu ; 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Using two models of LPS‐induced endotoxemia and cecal ligation and puncture (CLP)–induced sepsis, we investigated the effects of C1q/TNF‐related protein 4(CTRP4) on septic lethality and sepsis‐induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4‐expressing macrophages as the key cell type inhibiting LPS‐induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.
CTRP4 decreased the mortalities of mice and pathological lung injury in the endotoxic shock model. The molecular mechanism behind this phenomenon remains that CTRP4 inhibited TLR4 internalization and activated downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33080044</pmid><doi>10.1002/eji.202048617</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-0835-0198</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipokines - metabolism Adoptive transfer Animals Anti-Inflammatory Agents - metabolism Antibiotics Cecum Cells, Cultured Clinical trials CTRP4 Cytokine storm Cytokines Cytokines - metabolism Disease Models, Animal Endotoxemia Endotoxemia - chemically induced Endotoxemia - metabolism endotoxic Inflammation Inflammation - chemically induced Inflammation - metabolism Internalization Lethality Lipopolysaccharides Lipopolysaccharides - pharmacology LPS Lung Injury - chemically induced Lung Injury - metabolism macrophage Macrophages Macrophages - metabolism Mice Mice, Inbred C57BL Sepsis Septic shock Shock, Septic - chemically induced Shock, Septic - metabolism TLR4 TLR4 protein Toll-like receptors Tumor necrosis factor |
| title | CTRP4 acts as an anti‐inflammatory factor in macrophages and protects against endotoxic shock |
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