IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice.
<h4>Background</h4>The protective role of IL-11, an IL-6 family cytokine, has been implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its role has not been elucidated in liver IRI. This study was designed to evaluate the effects of IL-11 and its mechanism of act...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0126296 |
| _version_ | 1819112277238874112 |
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| author | Miao Zhu Bo Lu Qinhong Cao Zhenfeng Wu Zhe Xu Weisu Li Xuequan Yao Fukun Liu |
| author_facet | Miao Zhu Bo Lu Qinhong Cao Zhenfeng Wu Zhe Xu Weisu Li Xuequan Yao Fukun Liu |
| author_sort | Miao Zhu |
| collection | DOAJ |
| description | <h4>Background</h4>The protective role of IL-11, an IL-6 family cytokine, has been implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its role has not been elucidated in liver IRI. This study was designed to evaluate the effects of IL-11 and its mechanism of action on liver IRI in a mouse model.<h4>Methods</h4>A partial (70%) warm liver IRI was induced by interrupting the artery/portal vein blood supply to the left/middle liver lobes. IL-11 mRNA expression of ischemic liver after reperfusion was analyzed. Signal transducer and activator of transcription 3 (STAT3) was analyzed following IL-11 treatment in vivo and in vitro. Next, IL-11 was injected intraperitoneally (ip) 1 hour before ischemia. Liver injury was assessed based on serum alanine aminotransferase levels and histopathology. Apoptosis and inflammation were also determined in the ischemic liver. To analyze the role of STAT3 in IL-11 treatment, STAT3 siRNA or non-specific (NS) siRNA was used in vitro and in vivo.<h4>Results</h4>IL-11 mRNA expression was significantly increased after reperfusion in the ischemic liver. STAT3, as a target of IL-11, was activated in hepatocytes after IL-11 treatment in vivo and in vitro. Next, effects of IL-11/STAT3 signaling pathway were assessed in liver IRI, which showed IL-11 treatment significantly attenuated liver IRI, as evidenced by reduced hepatocellular function and hepatocellular necrosis/apoptosis. In addition, IL-11 treatment significantly inhibited the gene expressions of pro-inflammatory cytokines (TNF-α and IL-10) and chemokines (IP-10 and MCP-1). To determine the role of STAT3 in the hepatoprotective effects of IL-11, STAT3 siRNA or NS siRNA was used prior to IL-11 treatment. The results showed STAT3 knockdown abrogated the protective effects of IL-11 in vitro and in vivo.<h4>Conclusions</h4>This work provides first-time evidence for the protective effect of IL-11 treatment on hepatocyte in liver IRI, through the activation of the STAT3 pathway. |
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| id | doaj.art-c46c90e400574bcb88781a2134c64812 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:10:57Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-c46c90e400574bcb88781a2134c648122022-12-21T18:39:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012629610.1371/journal.pone.0126296IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice.Miao ZhuBo LuQinhong CaoZhenfeng WuZhe XuWeisu LiXuequan YaoFukun Liu<h4>Background</h4>The protective role of IL-11, an IL-6 family cytokine, has been implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its role has not been elucidated in liver IRI. This study was designed to evaluate the effects of IL-11 and its mechanism of action on liver IRI in a mouse model.<h4>Methods</h4>A partial (70%) warm liver IRI was induced by interrupting the artery/portal vein blood supply to the left/middle liver lobes. IL-11 mRNA expression of ischemic liver after reperfusion was analyzed. Signal transducer and activator of transcription 3 (STAT3) was analyzed following IL-11 treatment in vivo and in vitro. Next, IL-11 was injected intraperitoneally (ip) 1 hour before ischemia. Liver injury was assessed based on serum alanine aminotransferase levels and histopathology. Apoptosis and inflammation were also determined in the ischemic liver. To analyze the role of STAT3 in IL-11 treatment, STAT3 siRNA or non-specific (NS) siRNA was used in vitro and in vivo.<h4>Results</h4>IL-11 mRNA expression was significantly increased after reperfusion in the ischemic liver. STAT3, as a target of IL-11, was activated in hepatocytes after IL-11 treatment in vivo and in vitro. Next, effects of IL-11/STAT3 signaling pathway were assessed in liver IRI, which showed IL-11 treatment significantly attenuated liver IRI, as evidenced by reduced hepatocellular function and hepatocellular necrosis/apoptosis. In addition, IL-11 treatment significantly inhibited the gene expressions of pro-inflammatory cytokines (TNF-α and IL-10) and chemokines (IP-10 and MCP-1). To determine the role of STAT3 in the hepatoprotective effects of IL-11, STAT3 siRNA or NS siRNA was used prior to IL-11 treatment. The results showed STAT3 knockdown abrogated the protective effects of IL-11 in vitro and in vivo.<h4>Conclusions</h4>This work provides first-time evidence for the protective effect of IL-11 treatment on hepatocyte in liver IRI, through the activation of the STAT3 pathway.https://doi.org/10.1371/journal.pone.0126296 |
| spellingShingle | Miao Zhu Bo Lu Qinhong Cao Zhenfeng Wu Zhe Xu Weisu Li Xuequan Yao Fukun Liu IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. PLoS ONE |
| title | IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. |
| title_full | IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. |
| title_fullStr | IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. |
| title_full_unstemmed | IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. |
| title_short | IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice. |
| title_sort | il 11 attenuates liver ischemia reperfusion injury iri through stat3 signaling pathway in mice |
| url | https://doi.org/10.1371/journal.pone.0126296 |
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