MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts
Aim To investigate the effect of miR‐223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs). Methodology Human dental pulp tissue (HDPT) and HDPFs were obtained from impa...
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| Veröffentlicht in: | International endodontic journal 2021-02, Vol.54 (2), p.241-254 |
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| creator | Wang, D. Sun, S. Xue, Y. Qiu, J. Ye, T. Zhang, R. Song, B. He, W. Zhang, Y. Jiang, W. |
| description | Aim
To investigate the effect of miR‐223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs).
Methodology
Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR‐223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR‐223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase‐1, IL‐1β and IL‐18 was determined by qRT‐PCR and Western blotting, respectively. The release of IL‐1β and IL‐18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one‐way analysis of variance; P |
| doi_str_mv | 10.1111/iej.13413 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2478219823</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2478219823</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3883-7401a7dee8e40f7aeffb3a055ac5d3e0b952379da99c52c26fec41c102aff7813</originalsourceid><addsrcrecordid>eNp10LtOwzAYhmELgWg5DNwAssTEEPAhTpwRoQJFBaoCc-Qkv4urnLATUCUGLoFr5EowtLDhxYMffZZehA4oOaH-nBpYnFAeUr6BhpRHImAioZtoSGjIAyalGKAd5xaEEEE43UYDzpIoiqgcorcbk9tmdnv2-f7BGMc1zFVnXqBcYgvzvlQdODyZ3vtnUxd9DgU2tS5VVamusd_ItU3tPMqWuFN2Dp2p5_h2MptyL_FTX6kaF1B3qsRtX7ZYm8w2Walc5_bQllalg_31vYseL0YP51fB5O5yfH42CXIuJQ_ikFAVFwASQqJjBVpnXBEhVC4KDiRLBONxUqgkyQXLWaQhD2lOCVNax5LyXXS02m1t89yD69JF09vaf5myMJaMJpJxr45XygdxzoJOW2sqZZcpJel359R3Tn86e3u4XuyzCoo_-RvWg9MVeDUlLP9fSsej69XkFw-OiiE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2478219823</pqid></control><display><type>article</type><title>MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Wang, D. ; Sun, S. ; Xue, Y. ; Qiu, J. ; Ye, T. ; Zhang, R. ; Song, B. ; He, W. ; Zhang, Y. ; Jiang, W.</creator><creatorcontrib>Wang, D. ; Sun, S. ; Xue, Y. ; Qiu, J. ; Ye, T. ; Zhang, R. ; Song, B. ; He, W. ; Zhang, Y. ; Jiang, W.</creatorcontrib><description>Aim
To investigate the effect of miR‐223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs).
Methodology
Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR‐223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR‐223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase‐1, IL‐1β and IL‐18 was determined by qRT‐PCR and Western blotting, respectively. The release of IL‐1β and IL‐18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one‐way analysis of variance; P < 0.05 indicated statistical significance.
Results
A decrease in miR‐223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR‐223 in HDPFs. The miR‐223 inhibitor further promoted ATP plus LPS‐induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS‐induced group (P < 0.05). In contrast, the miR‐223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS‐induced group (P < 0.05).
Conclusion
MiR‐223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.</description><identifier>ISSN: 0143-2885</identifier><identifier>EISSN: 1365-2591</identifier><identifier>DOI: 10.1111/iej.13413</identifier><identifier>PMID: 32966618</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Caspase ; Computer applications ; Cytokines ; Dental Pulp ; Enzyme-linked immunosorbent assay ; Fibroblasts ; Gene expression ; human dental pulp fibroblasts ; Humans ; IL‐1β ; Inflammasomes ; Inflammation ; Interleukin-1beta ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; MicroRNAs ; miRNA ; miR‐223 ; Molars ; mRNA ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 ; pulpitis ; Western blotting</subject><ispartof>International endodontic journal, 2021-02, Vol.54 (2), p.241-254</ispartof><rights>2020 International Endodontic Journal. Published by John Wiley & Sons Ltd</rights><rights>2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-7401a7dee8e40f7aeffb3a055ac5d3e0b952379da99c52c26fec41c102aff7813</citedby><cites>FETCH-LOGICAL-c3883-7401a7dee8e40f7aeffb3a055ac5d3e0b952379da99c52c26fec41c102aff7813</cites><orcidid>0000-0002-6841-5021 ; 0000-0002-2213-9850</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fiej.13413$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fiej.13413$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32966618$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, D.</creatorcontrib><creatorcontrib>Sun, S.</creatorcontrib><creatorcontrib>Xue, Y.</creatorcontrib><creatorcontrib>Qiu, J.</creatorcontrib><creatorcontrib>Ye, T.</creatorcontrib><creatorcontrib>Zhang, R.</creatorcontrib><creatorcontrib>Song, B.</creatorcontrib><creatorcontrib>He, W.</creatorcontrib><creatorcontrib>Zhang, Y.</creatorcontrib><creatorcontrib>Jiang, W.</creatorcontrib><title>MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts</title><title>International endodontic journal</title><addtitle>Int Endod J</addtitle><description>Aim
To investigate the effect of miR‐223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs).
Methodology
Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR‐223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR‐223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase‐1, IL‐1β and IL‐18 was determined by qRT‐PCR and Western blotting, respectively. The release of IL‐1β and IL‐18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one‐way analysis of variance; P < 0.05 indicated statistical significance.
Results
A decrease in miR‐223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR‐223 in HDPFs. The miR‐223 inhibitor further promoted ATP plus LPS‐induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS‐induced group (P < 0.05). In contrast, the miR‐223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS‐induced group (P < 0.05).
Conclusion
MiR‐223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.</description><subject>Caspase</subject><subject>Computer applications</subject><subject>Cytokines</subject><subject>Dental Pulp</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>human dental pulp fibroblasts</subject><subject>Humans</subject><subject>IL‐1β</subject><subject>Inflammasomes</subject><subject>Inflammation</subject><subject>Interleukin-1beta</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>miR‐223</subject><subject>Molars</subject><subject>mRNA</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein</subject><subject>NLRP3</subject><subject>pulpitis</subject><subject>Western blotting</subject><issn>0143-2885</issn><issn>1365-2591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10LtOwzAYhmELgWg5DNwAssTEEPAhTpwRoQJFBaoCc-Qkv4urnLATUCUGLoFr5EowtLDhxYMffZZehA4oOaH-nBpYnFAeUr6BhpRHImAioZtoSGjIAyalGKAd5xaEEEE43UYDzpIoiqgcorcbk9tmdnv2-f7BGMc1zFVnXqBcYgvzvlQdODyZ3vtnUxd9DgU2tS5VVamusd_ItU3tPMqWuFN2Dp2p5_h2MptyL_FTX6kaF1B3qsRtX7ZYm8w2Walc5_bQllalg_31vYseL0YP51fB5O5yfH42CXIuJQ_ikFAVFwASQqJjBVpnXBEhVC4KDiRLBONxUqgkyQXLWaQhD2lOCVNax5LyXXS02m1t89yD69JF09vaf5myMJaMJpJxr45XygdxzoJOW2sqZZcpJel359R3Tn86e3u4XuyzCoo_-RvWg9MVeDUlLP9fSsej69XkFw-OiiE</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Wang, D.</creator><creator>Sun, S.</creator><creator>Xue, Y.</creator><creator>Qiu, J.</creator><creator>Ye, T.</creator><creator>Zhang, R.</creator><creator>Song, B.</creator><creator>He, W.</creator><creator>Zhang, Y.</creator><creator>Jiang, W.</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>K9.</scope><orcidid>https://orcid.org/0000-0002-6841-5021</orcidid><orcidid>https://orcid.org/0000-0002-2213-9850</orcidid></search><sort><creationdate>202102</creationdate><title>MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts</title><author>Wang, D. ; Sun, S. ; Xue, Y. ; Qiu, J. ; Ye, T. ; Zhang, R. ; Song, B. ; He, W. ; Zhang, Y. ; Jiang, W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3883-7401a7dee8e40f7aeffb3a055ac5d3e0b952379da99c52c26fec41c102aff7813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Caspase</topic><topic>Computer applications</topic><topic>Cytokines</topic><topic>Dental Pulp</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>human dental pulp fibroblasts</topic><topic>Humans</topic><topic>IL‐1β</topic><topic>Inflammasomes</topic><topic>Inflammation</topic><topic>Interleukin-1beta</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>miR‐223</topic><topic>Molars</topic><topic>mRNA</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein</topic><topic>NLRP3</topic><topic>pulpitis</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, D.</creatorcontrib><creatorcontrib>Sun, S.</creatorcontrib><creatorcontrib>Xue, Y.</creatorcontrib><creatorcontrib>Qiu, J.</creatorcontrib><creatorcontrib>Ye, T.</creatorcontrib><creatorcontrib>Zhang, R.</creatorcontrib><creatorcontrib>Song, B.</creatorcontrib><creatorcontrib>He, W.</creatorcontrib><creatorcontrib>Zhang, Y.</creatorcontrib><creatorcontrib>Jiang, W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>International endodontic journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, D.</au><au>Sun, S.</au><au>Xue, Y.</au><au>Qiu, J.</au><au>Ye, T.</au><au>Zhang, R.</au><au>Song, B.</au><au>He, W.</au><au>Zhang, Y.</au><au>Jiang, W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts</atitle><jtitle>International endodontic journal</jtitle><addtitle>Int Endod J</addtitle><date>2021-02</date><risdate>2021</risdate><volume>54</volume><issue>2</issue><spage>241</spage><epage>254</epage><pages>241-254</pages><issn>0143-2885</issn><eissn>1365-2591</eissn><abstract>Aim
To investigate the effect of miR‐223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokines IL‐1β and IL‐18 in human dental pulp fibroblasts (HDPFs).
Methodology
Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR‐223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR‐223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase‐1, IL‐1β and IL‐18 was determined by qRT‐PCR and Western blotting, respectively. The release of IL‐1β and IL‐18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one‐way analysis of variance; P < 0.05 indicated statistical significance.
Results
A decrease in miR‐223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR‐223 in HDPFs. The miR‐223 inhibitor further promoted ATP plus LPS‐induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS‐induced group (P < 0.05). In contrast, the miR‐223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS‐induced group (P < 0.05).
Conclusion
MiR‐223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32966618</pmid><doi>10.1111/iej.13413</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-6841-5021</orcidid><orcidid>https://orcid.org/0000-0002-2213-9850</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0143-2885 |
| ispartof | International endodontic journal, 2021-02, Vol.54 (2), p.241-254 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Caspase Computer applications Cytokines Dental Pulp Enzyme-linked immunosorbent assay Fibroblasts Gene expression human dental pulp fibroblasts Humans IL‐1β Inflammasomes Inflammation Interleukin-1beta Lipopolysaccharides Lipopolysaccharides - pharmacology MicroRNAs miRNA miR‐223 Molars mRNA NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 pulpitis Western blotting |
| title | MicroRNA‐223 negatively regulates LPS‐induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts |
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