IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis
Abstract Background Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a–e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through...
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| Veröffentlicht in: | Inflammatory bowel diseases 2021-01, Vol.27 (1), p.84-93 |
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| container_title | Inflammatory bowel diseases |
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| creator | Li, Yuan Chu, Hongxia Zhao, Mingsheng Li, Chaoze Guan, Yetong Guo, Chun Li, Yan Wang, Qun Shi, Yongyu Zhu, Faliang Zhang, Lining |
| description | Abstract
Background
Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a–e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis.
Methods
NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5′-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1β, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo.
Results
Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1β, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation.
Conclusion
Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.
In summary, IL-37d suppresses inflammasome activation through inhibiting NLRP3 transcription in a receptor-dependent manner. Further, IL-37d could alleviate DSS-induced colitis by inhibiting NLRP3 inflammasome activation. |
| doi_str_mv | 10.1093/ibd/izaa124 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2417403770</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A697884349</galeid><oup_id>10.1093/ibd/izaa124</oup_id><sourcerecordid>A697884349</sourcerecordid><originalsourceid>FETCH-LOGICAL-c387t-ee5b81e89a91ace75467d70765707468410cc040d5c7c54bf39d6256585d40753</originalsourceid><addsrcrecordid>eNp90d-LVCEUB3CJot22nnqPC0EEcXf1qld9HKZfC8O27G7P4ui5k-Fcb-qdmP763GYKgogDKvI5B_GL0HOCzwlW9MKv3YX_YQzp2AN0SjjtWyYZe1jPWMgWKyVP0JOcv2Lc1VKP0QntuOwUZ6douly1VLjmCjam-B2EfXMDmzmYArm5Wt1c0-YumTHb5Kfi49jsvKnCwlRiarfgfJWuuTbly3ezb8zomkUIsPO_Bry9vW396GZbyTIGX3x-ih4NJmR4dtzP0Of37-6WH9vVpw-Xy8WqtVSK0gLwtSQglVHEWBCc9cIJLHpeF9ZLRrC1mGHHrbCcrQeqXN_xnkvuGBacnqHXh7lTit9myEVvfbYQghkhzll3jAiGqRC40pcHujEBtB-HWJKx91wveiWkZJSpqs7_oWo52HobRxh8vf-r4c2hwaaYc4JBT8lvTdprgvV9cromp4_JVf3i-N55Xb_1j_0dVQWvDiDO038n_QQwFJ-M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417403770</pqid></control><display><type>article</type><title>IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis</title><source>OUP_牛津大学出版社现刊</source><creator>Li, Yuan ; Chu, Hongxia ; Zhao, Mingsheng ; Li, Chaoze ; Guan, Yetong ; Guo, Chun ; Li, Yan ; Wang, Qun ; Shi, Yongyu ; Zhu, Faliang ; Zhang, Lining</creator><creatorcontrib>Li, Yuan ; Chu, Hongxia ; Zhao, Mingsheng ; Li, Chaoze ; Guan, Yetong ; Guo, Chun ; Li, Yan ; Wang, Qun ; Shi, Yongyu ; Zhu, Faliang ; Zhang, Lining</creatorcontrib><description>Abstract
Background
Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a–e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis.
Methods
NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5′-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1β, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo.
Results
Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1β, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation.
Conclusion
Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.
In summary, IL-37d suppresses inflammasome activation through inhibiting NLRP3 transcription in a receptor-dependent manner. Further, IL-37d could alleviate DSS-induced colitis by inhibiting NLRP3 inflammasome activation.</description><identifier>ISSN: 1078-0998</identifier><identifier>EISSN: 1536-4844</identifier><identifier>DOI: 10.1093/ibd/izaa124</identifier><identifier>PMID: 32582954</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Analysis ; Colitis ; Dextran ; Enzyme-linked immunosorbent assay ; Ethylenediaminetetraacetic acid ; Genetic engineering ; Genetic transcription ; Interleukins ; Medical research ; Medicine, Experimental ; Recombinant proteins ; Sulfates</subject><ispartof>Inflammatory bowel diseases, 2021-01, Vol.27 (1), p.84-93</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020</rights><rights>2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-ee5b81e89a91ace75467d70765707468410cc040d5c7c54bf39d6256585d40753</citedby><cites>FETCH-LOGICAL-c387t-ee5b81e89a91ace75467d70765707468410cc040d5c7c54bf39d6256585d40753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32582954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Chu, Hongxia</creatorcontrib><creatorcontrib>Zhao, Mingsheng</creatorcontrib><creatorcontrib>Li, Chaoze</creatorcontrib><creatorcontrib>Guan, Yetong</creatorcontrib><creatorcontrib>Guo, Chun</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Wang, Qun</creatorcontrib><creatorcontrib>Shi, Yongyu</creatorcontrib><creatorcontrib>Zhu, Faliang</creatorcontrib><creatorcontrib>Zhang, Lining</creatorcontrib><title>IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis</title><title>Inflammatory bowel diseases</title><addtitle>Inflamm Bowel Dis</addtitle><description>Abstract
Background
Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a–e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis.
Methods
NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5′-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1β, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo.
Results
Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1β, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation.
Conclusion
Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.
In summary, IL-37d suppresses inflammasome activation through inhibiting NLRP3 transcription in a receptor-dependent manner. Further, IL-37d could alleviate DSS-induced colitis by inhibiting NLRP3 inflammasome activation.</description><subject>Analysis</subject><subject>Colitis</subject><subject>Dextran</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Genetic engineering</subject><subject>Genetic transcription</subject><subject>Interleukins</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Recombinant proteins</subject><subject>Sulfates</subject><issn>1078-0998</issn><issn>1536-4844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp90d-LVCEUB3CJot22nnqPC0EEcXf1qld9HKZfC8O27G7P4ui5k-Fcb-qdmP763GYKgogDKvI5B_GL0HOCzwlW9MKv3YX_YQzp2AN0SjjtWyYZe1jPWMgWKyVP0JOcv2Lc1VKP0QntuOwUZ6douly1VLjmCjam-B2EfXMDmzmYArm5Wt1c0-YumTHb5Kfi49jsvKnCwlRiarfgfJWuuTbly3ezb8zomkUIsPO_Bry9vW396GZbyTIGX3x-ih4NJmR4dtzP0Of37-6WH9vVpw-Xy8WqtVSK0gLwtSQglVHEWBCc9cIJLHpeF9ZLRrC1mGHHrbCcrQeqXN_xnkvuGBacnqHXh7lTit9myEVvfbYQghkhzll3jAiGqRC40pcHujEBtB-HWJKx91wveiWkZJSpqs7_oWo52HobRxh8vf-r4c2hwaaYc4JBT8lvTdprgvV9cromp4_JVf3i-N55Xb_1j_0dVQWvDiDO038n_QQwFJ-M</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Li, Yuan</creator><creator>Chu, Hongxia</creator><creator>Zhao, Mingsheng</creator><creator>Li, Chaoze</creator><creator>Guan, Yetong</creator><creator>Guo, Chun</creator><creator>Li, Yan</creator><creator>Wang, Qun</creator><creator>Shi, Yongyu</creator><creator>Zhu, Faliang</creator><creator>Zhang, Lining</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20210101</creationdate><title>IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis</title><author>Li, Yuan ; Chu, Hongxia ; Zhao, Mingsheng ; Li, Chaoze ; Guan, Yetong ; Guo, Chun ; Li, Yan ; Wang, Qun ; Shi, Yongyu ; Zhu, Faliang ; Zhang, Lining</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-ee5b81e89a91ace75467d70765707468410cc040d5c7c54bf39d6256585d40753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Colitis</topic><topic>Dextran</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Genetic engineering</topic><topic>Genetic transcription</topic><topic>Interleukins</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Recombinant proteins</topic><topic>Sulfates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Chu, Hongxia</creatorcontrib><creatorcontrib>Zhao, Mingsheng</creatorcontrib><creatorcontrib>Li, Chaoze</creatorcontrib><creatorcontrib>Guan, Yetong</creatorcontrib><creatorcontrib>Guo, Chun</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Wang, Qun</creatorcontrib><creatorcontrib>Shi, Yongyu</creatorcontrib><creatorcontrib>Zhu, Faliang</creatorcontrib><creatorcontrib>Zhang, Lining</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Inflammatory bowel diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yuan</au><au>Chu, Hongxia</au><au>Zhao, Mingsheng</au><au>Li, Chaoze</au><au>Guan, Yetong</au><au>Guo, Chun</au><au>Li, Yan</au><au>Wang, Qun</au><au>Shi, Yongyu</au><au>Zhu, Faliang</au><au>Zhang, Lining</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis</atitle><jtitle>Inflammatory bowel diseases</jtitle><addtitle>Inflamm Bowel Dis</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>27</volume><issue>1</issue><spage>84</spage><epage>93</epage><pages>84-93</pages><issn>1078-0998</issn><eissn>1536-4844</eissn><abstract>Abstract
Background
Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a–e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis.
Methods
NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5′-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1β, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo.
Results
Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1β, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation.
Conclusion
Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.
In summary, IL-37d suppresses inflammasome activation through inhibiting NLRP3 transcription in a receptor-dependent manner. Further, IL-37d could alleviate DSS-induced colitis by inhibiting NLRP3 inflammasome activation.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32582954</pmid><doi>10.1093/ibd/izaa124</doi><tpages>10</tpages></addata></record> |
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| ispartof | Inflammatory bowel diseases, 2021-01, Vol.27 (1), p.84-93 |
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| source | OUP_牛津大学出版社现刊 |
| subjects | Analysis Colitis Dextran Enzyme-linked immunosorbent assay Ethylenediaminetetraacetic acid Genetic engineering Genetic transcription Interleukins Medical research Medicine, Experimental Recombinant proteins Sulfates |
| title | IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis |
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