Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo
Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the devel...
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| Veröffentlicht in: | Archives of toxicology 2021-11, Vol.95 (11), p.3497-3513 |
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| creator | Li, Ziyin Chi, Huiqin Zhu, Wei Yang, Guangyu Song, Jia Mo, Lijun Zhang, Yitian Deng, Yudi Xu, Feifei Yang, Jiani He, Zhini Yang, Xingfen |
| description | Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl
2
(2–8 μM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1β and IL-18 (
P
|
| doi_str_mv | 10.1007/s00204-021-03157-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2579207571</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2579207571</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-75fe3bba337e59d0344e1f0a7c2365807d785f965b79d2dd7286beea25a925ab3</originalsourceid><addsrcrecordid>eNp9kE1OwzAQhS0EgvJzARbIEmvTsR3XyRIqCogCVYG15cROG9QkxU6KKnEyDsGZMISfHYvR6NnfvNE8hA4pnFAA2fcADCICjBLgVEjCNlCPRpwRkDzeRD3gERAhB3QH7Xr_BEBZnPBttMMjQYGxpIdeh9qURVviojJtZj12ttKLoPKFLkvdFHWF0zXWWVOsgqpmuJlbfDueTvgv5OvShmdXt7M5nt7d929OJ9f92xF5fzvDS93MX_Q6wHhVNK7GujKdWNX7aCvXC28PvvseehydPwwvyfju4mp4OiYZl6IhUuSWp6nmXFqRmHBVZGkOWmaMD0QM0shY5MlApDIxzBjJ4kFqrWZCJ6FSvoeOO9-lq59b6xv1VLcu3OkVEzJhIIWkgWIdlbnae2dztXRFqd1aUVCfgasucBUCV1-BKxaGjr6t27S05nfkJ-EA8A7w4auaWfe3-x_bD_eBi7I</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2579207571</pqid></control><display><type>article</type><title>Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo</title><source>MEDLINE</source><source>Springer Online Journals Complete</source><creator>Li, Ziyin ; Chi, Huiqin ; Zhu, Wei ; Yang, Guangyu ; Song, Jia ; Mo, Lijun ; Zhang, Yitian ; Deng, Yudi ; Xu, Feifei ; Yang, Jiani ; He, Zhini ; Yang, Xingfen</creator><creatorcontrib>Li, Ziyin ; Chi, Huiqin ; Zhu, Wei ; Yang, Guangyu ; Song, Jia ; Mo, Lijun ; Zhang, Yitian ; Deng, Yudi ; Xu, Feifei ; Yang, Jiani ; He, Zhini ; Yang, Xingfen</creatorcontrib><description>Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl
2
(2–8 μM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1β and IL-18 (
P
< 0.05). Knock-down of NLRP3 rescued the RPTEC/TERT1 cells from Cd-induced inflammatory damage. Cd activated the MAPK/NF-κB signaling pathway in RPTEC/TERT1 cells (
P
< 0.05). In addition, treatment with N-acetylcysteine (NAC) improved inflammation and blocked the upregulation of the MAPK/NF-κB signaling pathway. Pre-treatment with MAPK and NF-κB inhibitors also suppressed NLRP3 inflammasome activation (
P
< 0.05). Moreover, CdCl
2
(25–00 mg/L) stimulated the MAPK/NF-κB signaling pathway, activated the NLRP3 inflammasome, and increased inflammatory response (
P
< 0.05) leading to renal injury in rats. Exposure to cadmium elevated serum levels of NLRP3 and IL-1β in populations (
P
< 0.05). Further analysis found that serum NLRP3 and IL-1β levels were positively correlated with urine cadmium (UCd) and urine N-acetyl-β-D-glucosaminidase (UNAG). Overall, Cd induced renal inflammation through the ROS/MAPK/NF-κB signaling pathway by activating the NLRP3 inflammasome. Our research thus provides new insights into the molecular mechanism that NLRP3 contributes to Cd-induced kidney damage.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-021-03157-2</identifier><identifier>PMID: 34510229</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acetylcysteine ; Acute Kidney Injury - chemically induced ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cadmium ; Cadmium - toxicity ; Cadmium - urine ; Cadmium chloride ; Cell Line, Transformed ; Damage ; Environmental Health ; Epithelial cells ; Epithelium ; Female ; Glucosaminidase ; Humans ; IL-1β ; Inflammasomes ; Inflammation ; Inflammation - etiology ; Inflammatory response ; Inorganic Compounds ; Interleukin 18 ; Kidney - drug effects ; Kidney - pathology ; Kidney Tubules, Proximal ; Kidneys ; Kinases ; MAP kinase ; Mitogen-Activated Protein Kinase Kinases - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Occupational Medicine/Industrial Medicine ; Oxidative stress ; Pathogenesis ; Pharmacology/Toxicology ; Pyrin protein ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species - metabolism ; Serum levels ; Signal Transduction ; Signaling ; Telomerase</subject><ispartof>Archives of toxicology, 2021-11, Vol.95 (11), p.3497-3513</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-75fe3bba337e59d0344e1f0a7c2365807d785f965b79d2dd7286beea25a925ab3</citedby><cites>FETCH-LOGICAL-c375t-75fe3bba337e59d0344e1f0a7c2365807d785f965b79d2dd7286beea25a925ab3</cites><orcidid>0000-0001-5806-4507</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00204-021-03157-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00204-021-03157-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34510229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ziyin</creatorcontrib><creatorcontrib>Chi, Huiqin</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Yang, Guangyu</creatorcontrib><creatorcontrib>Song, Jia</creatorcontrib><creatorcontrib>Mo, Lijun</creatorcontrib><creatorcontrib>Zhang, Yitian</creatorcontrib><creatorcontrib>Deng, Yudi</creatorcontrib><creatorcontrib>Xu, Feifei</creatorcontrib><creatorcontrib>Yang, Jiani</creatorcontrib><creatorcontrib>He, Zhini</creatorcontrib><creatorcontrib>Yang, Xingfen</creatorcontrib><title>Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><addtitle>Arch Toxicol</addtitle><description>Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl
2
(2–8 μM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1β and IL-18 (
P
< 0.05). Knock-down of NLRP3 rescued the RPTEC/TERT1 cells from Cd-induced inflammatory damage. Cd activated the MAPK/NF-κB signaling pathway in RPTEC/TERT1 cells (
P
< 0.05). In addition, treatment with N-acetylcysteine (NAC) improved inflammation and blocked the upregulation of the MAPK/NF-κB signaling pathway. Pre-treatment with MAPK and NF-κB inhibitors also suppressed NLRP3 inflammasome activation (
P
< 0.05). Moreover, CdCl
2
(25–00 mg/L) stimulated the MAPK/NF-κB signaling pathway, activated the NLRP3 inflammasome, and increased inflammatory response (
P
< 0.05) leading to renal injury in rats. Exposure to cadmium elevated serum levels of NLRP3 and IL-1β in populations (
P
< 0.05). Further analysis found that serum NLRP3 and IL-1β levels were positively correlated with urine cadmium (UCd) and urine N-acetyl-β-D-glucosaminidase (UNAG). Overall, Cd induced renal inflammation through the ROS/MAPK/NF-κB signaling pathway by activating the NLRP3 inflammasome. Our research thus provides new insights into the molecular mechanism that NLRP3 contributes to Cd-induced kidney damage.</description><subject>Acetylcysteine</subject><subject>Acute Kidney Injury - chemically induced</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cadmium</subject><subject>Cadmium - toxicity</subject><subject>Cadmium - urine</subject><subject>Cadmium chloride</subject><subject>Cell Line, Transformed</subject><subject>Damage</subject><subject>Environmental Health</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Female</subject><subject>Glucosaminidase</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Inflammasomes</subject><subject>Inflammation</subject><subject>Inflammation - etiology</subject><subject>Inflammatory response</subject><subject>Inorganic Compounds</subject><subject>Interleukin 18</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Kidney Tubules, Proximal</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Oxidative stress</subject><subject>Pathogenesis</subject><subject>Pharmacology/Toxicology</subject><subject>Pyrin protein</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Serum levels</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Telomerase</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kE1OwzAQhS0EgvJzARbIEmvTsR3XyRIqCogCVYG15cROG9QkxU6KKnEyDsGZMISfHYvR6NnfvNE8hA4pnFAA2fcADCICjBLgVEjCNlCPRpwRkDzeRD3gERAhB3QH7Xr_BEBZnPBttMMjQYGxpIdeh9qURVviojJtZj12ttKLoPKFLkvdFHWF0zXWWVOsgqpmuJlbfDueTvgv5OvShmdXt7M5nt7d929OJ9f92xF5fzvDS93MX_Q6wHhVNK7GujKdWNX7aCvXC28PvvseehydPwwvyfju4mp4OiYZl6IhUuSWp6nmXFqRmHBVZGkOWmaMD0QM0shY5MlApDIxzBjJ4kFqrWZCJ6FSvoeOO9-lq59b6xv1VLcu3OkVEzJhIIWkgWIdlbnae2dztXRFqd1aUVCfgasucBUCV1-BKxaGjr6t27S05nfkJ-EA8A7w4auaWfe3-x_bD_eBi7I</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Li, Ziyin</creator><creator>Chi, Huiqin</creator><creator>Zhu, Wei</creator><creator>Yang, Guangyu</creator><creator>Song, Jia</creator><creator>Mo, Lijun</creator><creator>Zhang, Yitian</creator><creator>Deng, Yudi</creator><creator>Xu, Feifei</creator><creator>Yang, Jiani</creator><creator>He, Zhini</creator><creator>Yang, Xingfen</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0001-5806-4507</orcidid></search><sort><creationdate>20211101</creationdate><title>Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo</title><author>Li, Ziyin ; Chi, Huiqin ; Zhu, Wei ; Yang, Guangyu ; Song, Jia ; Mo, Lijun ; Zhang, Yitian ; Deng, Yudi ; Xu, Feifei ; Yang, Jiani ; He, Zhini ; Yang, Xingfen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-75fe3bba337e59d0344e1f0a7c2365807d785f965b79d2dd7286beea25a925ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetylcysteine</topic><topic>Acute Kidney Injury - chemically induced</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cadmium</topic><topic>Cadmium - toxicity</topic><topic>Cadmium - urine</topic><topic>Cadmium chloride</topic><topic>Cell Line, Transformed</topic><topic>Damage</topic><topic>Environmental Health</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Female</topic><topic>Glucosaminidase</topic><topic>Humans</topic><topic>IL-1β</topic><topic>Inflammasomes</topic><topic>Inflammation</topic><topic>Inflammation - etiology</topic><topic>Inflammatory response</topic><topic>Inorganic Compounds</topic><topic>Interleukin 18</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Kidney Tubules, Proximal</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Oxidative stress</topic><topic>Pathogenesis</topic><topic>Pharmacology/Toxicology</topic><topic>Pyrin protein</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Serum levels</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Telomerase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ziyin</creatorcontrib><creatorcontrib>Chi, Huiqin</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Yang, Guangyu</creatorcontrib><creatorcontrib>Song, Jia</creatorcontrib><creatorcontrib>Mo, Lijun</creatorcontrib><creatorcontrib>Zhang, Yitian</creatorcontrib><creatorcontrib>Deng, Yudi</creatorcontrib><creatorcontrib>Xu, Feifei</creatorcontrib><creatorcontrib>Yang, Jiani</creatorcontrib><creatorcontrib>He, Zhini</creatorcontrib><creatorcontrib>Yang, Xingfen</creatorcontrib><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>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology 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>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Research Library (Corporate)</collection><collection>Environmental Science 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>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><jtitle>Archives of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ziyin</au><au>Chi, Huiqin</au><au>Zhu, Wei</au><au>Yang, Guangyu</au><au>Song, Jia</au><au>Mo, Lijun</au><au>Zhang, Yitian</au><au>Deng, Yudi</au><au>Xu, Feifei</au><au>Yang, Jiani</au><au>He, Zhini</au><au>Yang, Xingfen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo</atitle><jtitle>Archives of toxicology</jtitle><stitle>Arch Toxicol</stitle><addtitle>Arch Toxicol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>95</volume><issue>11</issue><spage>3497</spage><epage>3513</epage><pages>3497-3513</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><abstract>Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl
2
(2–8 μM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1β and IL-18 (
P
< 0.05). Knock-down of NLRP3 rescued the RPTEC/TERT1 cells from Cd-induced inflammatory damage. Cd activated the MAPK/NF-κB signaling pathway in RPTEC/TERT1 cells (
P
< 0.05). In addition, treatment with N-acetylcysteine (NAC) improved inflammation and blocked the upregulation of the MAPK/NF-κB signaling pathway. Pre-treatment with MAPK and NF-κB inhibitors also suppressed NLRP3 inflammasome activation (
P
< 0.05). Moreover, CdCl
2
(25–00 mg/L) stimulated the MAPK/NF-κB signaling pathway, activated the NLRP3 inflammasome, and increased inflammatory response (
P
< 0.05) leading to renal injury in rats. Exposure to cadmium elevated serum levels of NLRP3 and IL-1β in populations (
P
< 0.05). Further analysis found that serum NLRP3 and IL-1β levels were positively correlated with urine cadmium (UCd) and urine N-acetyl-β-D-glucosaminidase (UNAG). Overall, Cd induced renal inflammation through the ROS/MAPK/NF-κB signaling pathway by activating the NLRP3 inflammasome. Our research thus provides new insights into the molecular mechanism that NLRP3 contributes to Cd-induced kidney damage.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34510229</pmid><doi>10.1007/s00204-021-03157-2</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-5806-4507</orcidid></addata></record> |
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| ispartof | Archives of toxicology, 2021-11, Vol.95 (11), p.3497-3513 |
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| subjects | Acetylcysteine Acute Kidney Injury - chemically induced Animals Biomedical and Life Sciences Biomedicine Cadmium Cadmium - toxicity Cadmium - urine Cadmium chloride Cell Line, Transformed Damage Environmental Health Epithelial cells Epithelium Female Glucosaminidase Humans IL-1β Inflammasomes Inflammation Inflammation - etiology Inflammatory response Inorganic Compounds Interleukin 18 Kidney - drug effects Kidney - pathology Kidney Tubules, Proximal Kidneys Kinases MAP kinase Mitogen-Activated Protein Kinase Kinases - metabolism NF-kappa B - metabolism NF-κB protein NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Occupational Medicine/Industrial Medicine Oxidative stress Pathogenesis Pharmacology/Toxicology Pyrin protein Rats Rats, Sprague-Dawley Reactive Oxygen Species - metabolism Serum levels Signal Transduction Signaling Telomerase |
| title | Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo |
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