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Conference Paper: Knockout Attenuates Inflammatory Response and Mitochondrial Dysfunction after Hepatic Ischemia-reperfusion Injury
Title | Knockout Attenuates Inflammatory Response and Mitochondrial Dysfunction after Hepatic Ischemia-reperfusion Injury |
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Authors | |
Issue Date | 2017 |
Citation | The 2017 Joint International Congress of ILTS, ELITA & LICAGE, Prague, Czech Republic, 24-27 May 2017 How to Cite? |
Abstract | Background: Ischemia-reperfusion (IR) injury is an inevitable consequence during liver transplantation. IL-17a initiates mitochondrial permeability transition pore (mPTP) opening in human platelets. Onset of mPTP plays a pivotal role on IR injury by inducing apoptotic and necrotic cell death. We aimed to investigate the role of IL-17a on mitochondria-driven hepatocyte apoptosis after IR injury.
Methods: The association between IL-17a expression and inflammatory response was analyzed both in human and rat liver transplantation. Wild-type (WT) and IL-17a knockout (KO) mice fed with high fat diet were subject to hepatic IR injury and major hepatectomy. Mitochondrial depolarization in hepatocytes was observed in live mice longitudinally using intra-vital imaging system. The cell adhesion and migration capacity was compared between the primary bone marrow neutrophils isolated from WT and IL-17a KO mice when co-cultured with liver sinusoidal endothelial cells.
Results: Serum IL-17a was significantly increased by 1.9 and 2.7 folds in normal graft and fatty graft respectively after human (Fig.A p=0.014) and rat (p=0.042) liver transplantation. It had a positive correlation with pro-inflammatory cytokines and serum transaminase levels. In our mouse hepatic IR injury model, knockout of IL-17a notably attenuated pro-inflammatory cytokines expression (Fig.B), neutrophils infiltration (Fig.C) and hepatocytes apoptosis (Fig.D) in fatty liver. Less mitochondrial depolarization (mPTP opening) in hepatocytes was observed in IL-17a knockout mice compared with wild-type mice (Fig.E 8% vs 30%) both in normal and fatty liver. Increased mitochondrial reactive oxygen species (mROS), phosphorylation of NF-?B and MAPK after hepatic IR injury could be suppressed by knockout of IL-17a (Fig.F). In vitro, IL-17a deficiency decreased neutrophils migration and adhesion activity in response to liver sinusoidal endothelial cells.
Conclusions: Knockout of IL-17a protected fatty liver against IR injury through suppression of inflammatory response and improvement of mitochondrial function. |
Persistent Identifier | http://hdl.handle.net/10722/245650 |
DC Field | Value | Language |
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dc.contributor.author | Yang, X | - |
dc.contributor.author | Li, C | - |
dc.contributor.author | Liu, J | - |
dc.contributor.author | Liu, H | - |
dc.contributor.author | MA, YY | - |
dc.contributor.author | Ng, KTP | - |
dc.contributor.author | Lo, CM | - |
dc.contributor.author | Man, K | - |
dc.date.accessioned | 2017-09-18T02:14:29Z | - |
dc.date.available | 2017-09-18T02:14:29Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | The 2017 Joint International Congress of ILTS, ELITA & LICAGE, Prague, Czech Republic, 24-27 May 2017 | - |
dc.identifier.uri | http://hdl.handle.net/10722/245650 | - |
dc.description.abstract | Background: Ischemia-reperfusion (IR) injury is an inevitable consequence during liver transplantation. IL-17a initiates mitochondrial permeability transition pore (mPTP) opening in human platelets. Onset of mPTP plays a pivotal role on IR injury by inducing apoptotic and necrotic cell death. We aimed to investigate the role of IL-17a on mitochondria-driven hepatocyte apoptosis after IR injury. Methods: The association between IL-17a expression and inflammatory response was analyzed both in human and rat liver transplantation. Wild-type (WT) and IL-17a knockout (KO) mice fed with high fat diet were subject to hepatic IR injury and major hepatectomy. Mitochondrial depolarization in hepatocytes was observed in live mice longitudinally using intra-vital imaging system. The cell adhesion and migration capacity was compared between the primary bone marrow neutrophils isolated from WT and IL-17a KO mice when co-cultured with liver sinusoidal endothelial cells. Results: Serum IL-17a was significantly increased by 1.9 and 2.7 folds in normal graft and fatty graft respectively after human (Fig.A p=0.014) and rat (p=0.042) liver transplantation. It had a positive correlation with pro-inflammatory cytokines and serum transaminase levels. In our mouse hepatic IR injury model, knockout of IL-17a notably attenuated pro-inflammatory cytokines expression (Fig.B), neutrophils infiltration (Fig.C) and hepatocytes apoptosis (Fig.D) in fatty liver. Less mitochondrial depolarization (mPTP opening) in hepatocytes was observed in IL-17a knockout mice compared with wild-type mice (Fig.E 8% vs 30%) both in normal and fatty liver. Increased mitochondrial reactive oxygen species (mROS), phosphorylation of NF-?B and MAPK after hepatic IR injury could be suppressed by knockout of IL-17a (Fig.F). In vitro, IL-17a deficiency decreased neutrophils migration and adhesion activity in response to liver sinusoidal endothelial cells. Conclusions: Knockout of IL-17a protected fatty liver against IR injury through suppression of inflammatory response and improvement of mitochondrial function. | - |
dc.language | eng | - |
dc.relation.ispartof | The 2017 Joint International Congress of ILTS, ELITA & LICAGE | - |
dc.title | Knockout Attenuates Inflammatory Response and Mitochondrial Dysfunction after Hepatic Ischemia-reperfusion Injury | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Yang, X: dryangxx@hku.hk | - |
dc.identifier.email | Liu, H: liuhui25@hku.hk | - |
dc.identifier.email | Ng, KTP: ledodes@hku.hk | - |
dc.identifier.email | Lo, CM: chungmlo@hkucc.hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.authority | Ng, KTP=rp01720 | - |
dc.identifier.authority | Lo, CM=rp00412 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.hkuros | 278246 | - |
dc.publisher.place | Prague, Czech Republic | - |