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Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways
AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated...
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| Published in: | World journal of gastroenterology : WJG 2015-03, Vol.21 (10), p.2937-2948 |
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| container_title | World journal of gastroenterology : WJG |
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| creator | Huang, Han-Fei Zeng, Zhong Wang, Kun-Hua Zhang, Hai-Yan Wang, Shuai Zhou, Wen-Xiang Wang, Zhan-Bo Xu, Wang-Gang Duan, Jian |
| description | AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats. |
| doi_str_mv | 10.3748/wjg.v21.i10.2937 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4356913</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>90888889504849534948484949</cqvip_id><sourcerecordid>1664444525</sourcerecordid><originalsourceid>FETCH-LOGICAL-c398t-111584195bf9882854a199ba8cc5255dabac1507e79bf1188fdee3a8a9d1c5683</originalsourceid><addsrcrecordid>eNpVkU2P0zAQhi0EYsvCnRPykUtafzb2BQmtgF2pEhJaztYkmaSuEqdrJy3997jaUi1z8Izsd16P5iHkI2dLWSqzOu665UHwpc8XwsryFVkIwW0hjGKvyYIzVhZWivKGvEtpx5iQUou35Ebo0jBh-YIc73FAOv45dRggYcHpPo4T1lOiESba-wNGCh34kCZ6hDhQn-otDh5WEfcY2zn5MVAfdnM80YMH-rj5JVb5UMUUfddhxIYm3wXofejoHqbtEU7pPXnTQp_wwyXfkt_fvz3e3Rebnz8e7r5uilpaMxWcc20Ut7pqrTHCaAXc2gpMXWuhdQMV1FyzEktbtZwb0zaIEgzYhtd6beQt-fLsu5-rAZsawxShd_voB4gnN4J3_78Ev3XdeHBK6rXlMht8vhjE8WnGNLkhbwD7HgKOc3J8vVY58jRZyp6ldRxTithev-HMnXm5zMtlXi7zcmdeueXTy_GuDf8AZYG8eG7H0D3lFV41lplzWM2UUVZLZXPOlbLyL36mpFY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1664444525</pqid></control><display><type>article</type><title>Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways</title><source>PubMed Central</source><creator>Huang, Han-Fei ; Zeng, Zhong ; Wang, Kun-Hua ; Zhang, Hai-Yan ; Wang, Shuai ; Zhou, Wen-Xiang ; Wang, Zhan-Bo ; Xu, Wang-Gang ; Duan, Jian</creator><creatorcontrib>Huang, Han-Fei ; Zeng, Zhong ; Wang, Kun-Hua ; Zhang, Hai-Yan ; Wang, Shuai ; Zhou, Wen-Xiang ; Wang, Zhan-Bo ; Xu, Wang-Gang ; Duan, Jian</creatorcontrib><description>AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.</description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.v21.i10.2937</identifier><identifier>PMID: 25780291</identifier><language>eng</language><publisher>United States: Baishideng Publishing Group Inc</publisher><subject>Adaptor Proteins, Vesicular Transport - metabolism ; Animals ; Basic Study ; Cytoprotection ; Disease Models, Animal ; Enzyme Inhibitors - pharmacology ; Heme ; Heme Oxygenase (Decyclizing) - antagonists & inhibitors ; Heme Oxygenase (Decyclizing) - metabolism ; injury;Toll ; Liver - drug effects ; Liver - enzymology ; Liver - immunology ; Liver - pathology ; Male ; Myeloid Differentiation Factor 88 - metabolism ; oxygenase-1;Ischemia ; Protoporphyrins - pharmacology ; Rats, Sprague-Dawley ; reperfusion ; Reperfusion Injury - enzymology ; Reperfusion Injury - etiology ; Reperfusion Injury - immunology ; Reperfusion Injury - pathology ; Reperfusion Injury - prevention & control ; Signal Transduction - drug effects ; Toll-Like Receptor 2 - drug effects ; Toll-Like Receptor 2 - metabolism ; Toll-Like Receptor 4 - drug effects ; Toll-Like Receptor 4 - metabolism ; Warm Ischemia - adverse effects</subject><ispartof>World journal of gastroenterology : WJG, 2015-03, Vol.21 (10), p.2937-2948</ispartof><rights>The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-111584195bf9882854a199ba8cc5255dabac1507e79bf1188fdee3a8a9d1c5683</citedby><cites>FETCH-LOGICAL-c398t-111584195bf9882854a199ba8cc5255dabac1507e79bf1188fdee3a8a9d1c5683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/84123X/84123X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356913/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356913/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,730,783,787,888,27938,27939,53806,53808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25780291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Han-Fei</creatorcontrib><creatorcontrib>Zeng, Zhong</creatorcontrib><creatorcontrib>Wang, Kun-Hua</creatorcontrib><creatorcontrib>Zhang, Hai-Yan</creatorcontrib><creatorcontrib>Wang, Shuai</creatorcontrib><creatorcontrib>Zhou, Wen-Xiang</creatorcontrib><creatorcontrib>Wang, Zhan-Bo</creatorcontrib><creatorcontrib>Xu, Wang-Gang</creatorcontrib><creatorcontrib>Duan, Jian</creatorcontrib><title>Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways</title><title>World journal of gastroenterology : WJG</title><addtitle>World Journal of Gastroenterology</addtitle><description>AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.</description><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>Animals</subject><subject>Basic Study</subject><subject>Cytoprotection</subject><subject>Disease Models, Animal</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Heme</subject><subject>Heme Oxygenase (Decyclizing) - antagonists & inhibitors</subject><subject>Heme Oxygenase (Decyclizing) - metabolism</subject><subject>injury;Toll</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - immunology</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Myeloid Differentiation Factor 88 - metabolism</subject><subject>oxygenase-1;Ischemia</subject><subject>Protoporphyrins - pharmacology</subject><subject>Rats, Sprague-Dawley</subject><subject>reperfusion</subject><subject>Reperfusion Injury - enzymology</subject><subject>Reperfusion Injury - etiology</subject><subject>Reperfusion Injury - immunology</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Signal Transduction - drug effects</subject><subject>Toll-Like Receptor 2 - drug effects</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Toll-Like Receptor 4 - drug effects</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Warm Ischemia - adverse effects</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVkU2P0zAQhi0EYsvCnRPykUtafzb2BQmtgF2pEhJaztYkmaSuEqdrJy3997jaUi1z8Izsd16P5iHkI2dLWSqzOu665UHwpc8XwsryFVkIwW0hjGKvyYIzVhZWivKGvEtpx5iQUou35Ebo0jBh-YIc73FAOv45dRggYcHpPo4T1lOiESba-wNGCh34kCZ6hDhQn-otDh5WEfcY2zn5MVAfdnM80YMH-rj5JVb5UMUUfddhxIYm3wXofejoHqbtEU7pPXnTQp_wwyXfkt_fvz3e3Rebnz8e7r5uilpaMxWcc20Ut7pqrTHCaAXc2gpMXWuhdQMV1FyzEktbtZwb0zaIEgzYhtd6beQt-fLsu5-rAZsawxShd_voB4gnN4J3_78Ev3XdeHBK6rXlMht8vhjE8WnGNLkhbwD7HgKOc3J8vVY58jRZyp6ldRxTithev-HMnXm5zMtlXi7zcmdeueXTy_GuDf8AZYG8eG7H0D3lFV41lplzWM2UUVZLZXPOlbLyL36mpFY</recordid><startdate>20150314</startdate><enddate>20150314</enddate><creator>Huang, Han-Fei</creator><creator>Zeng, Zhong</creator><creator>Wang, Kun-Hua</creator><creator>Zhang, Hai-Yan</creator><creator>Wang, Shuai</creator><creator>Zhou, Wen-Xiang</creator><creator>Wang, Zhan-Bo</creator><creator>Xu, Wang-Gang</creator><creator>Duan, Jian</creator><general>Baishideng Publishing Group Inc</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150314</creationdate><title>Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways</title><author>Huang, Han-Fei ; Zeng, Zhong ; Wang, Kun-Hua ; Zhang, Hai-Yan ; Wang, Shuai ; Zhou, Wen-Xiang ; Wang, Zhan-Bo ; Xu, Wang-Gang ; Duan, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-111584195bf9882854a199ba8cc5255dabac1507e79bf1188fdee3a8a9d1c5683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptor Proteins, Vesicular Transport - metabolism</topic><topic>Animals</topic><topic>Basic Study</topic><topic>Cytoprotection</topic><topic>Disease Models, Animal</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Heme</topic><topic>Heme Oxygenase (Decyclizing) - antagonists & inhibitors</topic><topic>Heme Oxygenase (Decyclizing) - metabolism</topic><topic>injury;Toll</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - immunology</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Myeloid Differentiation Factor 88 - metabolism</topic><topic>oxygenase-1;Ischemia</topic><topic>Protoporphyrins - pharmacology</topic><topic>Rats, Sprague-Dawley</topic><topic>reperfusion</topic><topic>Reperfusion Injury - enzymology</topic><topic>Reperfusion Injury - etiology</topic><topic>Reperfusion Injury - immunology</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Signal Transduction - drug effects</topic><topic>Toll-Like Receptor 2 - drug effects</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Toll-Like Receptor 4 - drug effects</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Warm Ischemia - adverse effects</topic><toplevel>online_resources</toplevel><creatorcontrib>Huang, Han-Fei</creatorcontrib><creatorcontrib>Zeng, Zhong</creatorcontrib><creatorcontrib>Wang, Kun-Hua</creatorcontrib><creatorcontrib>Zhang, Hai-Yan</creatorcontrib><creatorcontrib>Wang, Shuai</creatorcontrib><creatorcontrib>Zhou, Wen-Xiang</creatorcontrib><creatorcontrib>Wang, Zhan-Bo</creatorcontrib><creatorcontrib>Xu, Wang-Gang</creatorcontrib><creatorcontrib>Duan, Jian</creatorcontrib><collection>维普_期刊</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>维普中文期刊数据库</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Han-Fei</au><au>Zeng, Zhong</au><au>Wang, Kun-Hua</au><au>Zhang, Hai-Yan</au><au>Wang, Shuai</au><au>Zhou, Wen-Xiang</au><au>Wang, Zhan-Bo</au><au>Xu, Wang-Gang</au><au>Duan, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World Journal of Gastroenterology</addtitle><date>2015-03-14</date><risdate>2015</risdate><volume>21</volume><issue>10</issue><spage>2937</spage><epage>2948</epage><pages>2937-2948</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><notes>Han-Fei Huang;Zhong Zeng;Kun-Hua Wang;Hai-Yan Zhang;Shuai Wang;Wen-Xiang Zhou;Zhan-Bo Wang;Wang-Gang Xu;Jian Duan;Organ Transplantation Center,the First Affiliated Hospital of Kunming Medical University</notes><notes>Heme oxygenase-1;Ischemia reperfusion injury;Toll-</notes><notes>AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Telephone: +86-871-65324888 Fax: +86-871-65359202</notes><notes>Author contributions: Huang HF and Zeng Z contributed equally to this work; Huang HF, Zhang HY and Wang S performed the majority of experiments; Zhou WX and Wang ZB performed data analysis; Xu WG and Duan J were involved in editing the manuscript; Wang KH designed the study.</notes><notes>Correspondence to: Zhong Zeng, MD, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunnan Province, China. zzong@medmail.com.cn</notes><abstract>AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.</abstract><cop>United States</cop><pub>Baishideng Publishing Group Inc</pub><pmid>25780291</pmid><doi>10.3748/wjg.v21.i10.2937</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1007-9327 2219-2840 |
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| subjects | Adaptor Proteins, Vesicular Transport - metabolism Animals Basic Study Cytoprotection Disease Models, Animal Enzyme Inhibitors - pharmacology Heme Heme Oxygenase (Decyclizing) - antagonists & inhibitors Heme Oxygenase (Decyclizing) - metabolism injury Toll Liver - drug effects Liver - enzymology Liver - immunology Liver - pathology Male Myeloid Differentiation Factor 88 - metabolism oxygenase-1 Ischemia Protoporphyrins - pharmacology Rats, Sprague-Dawley reperfusion Reperfusion Injury - enzymology Reperfusion Injury - etiology Reperfusion Injury - immunology Reperfusion Injury - pathology Reperfusion Injury - prevention & control Signal Transduction - drug effects Toll-Like Receptor 2 - drug effects Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - drug effects Toll-Like Receptor 4 - metabolism Warm Ischemia - adverse effects |
| title | Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-02T14%3A29%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Heme%20oxygenase-1%20protects%20rat%20liver%20against%20warm%20ischemia/reperfusion%20injury%20via%20TLR2/TLR4-triggered%20signaling%20pathways&rft.jtitle=World%20journal%20of%20gastroenterology%20:%20WJG&rft.au=Huang,%20Han-Fei&rft.date=2015-03-14&rft.volume=21&rft.issue=10&rft.spage=2937&rft.epage=2948&rft.pages=2937-2948&rft.issn=1007-9327&rft.eissn=2219-2840&rft_id=info:doi/10.3748/wjg.v21.i10.2937&rft_dat=%3Cproquest_pubme%3E1664444525%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c398t-111584195bf9882854a199ba8cc5255dabac1507e79bf1188fdee3a8a9d1c5683%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1664444525&rft_id=info:pmid/25780291&rft_cqvip_id=90888889504849534948484949&rfr_iscdi=true |