PMID- 25780291 OWN - NLM STAT- MEDLINE DCOM- 20151015 LR - 20200914 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 21 IP - 10 DP - 2015 Mar 14 TI - Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways. PG - 2937-48 LID - 10.3748/wjg.v21.i10.2937 [doi] AB - AIM: To investigate the efficacy and molecular mechanisms 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 75 min, followed by 6 h of reperfusion. Rats were treated with saline, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP) 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-beta (TRIF) and anti-myeloid differentiation factor 88 (MyD88), 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 well-preserved tissue architecture. In comparison with ZnPP livers 6 h after surgery, CoPP 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 kinase 1 protein levels of rats treated with CoPP significantly reduced in TRIF-immunoprecipitated complex, as compared with ZnPP treatment. In addition, pretreatment with CoPP reduced the expression levels of TLR2, TLR4, IL-1R-associated kinase (IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in MyD88-immunoprecipitated complex. The inflammatory cytokines and chemokines mRNA expression rapidly decreased in CoPP-pretreated liver, compared with the ZnPP-treated group. However, the expression of negative regulators Toll-interacting protein, suppressor of cytokine signaling-1, IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in CoPP treatment rats were markedly up-regulated as compared with ZnPP-treated rats. CONCLUSION: HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered MyD88- and TRIF-dependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats. FAU - Huang, Han-Fei AU - Huang HF AD - 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, Kunming 650032, Yunnan Province, China. FAU - Zeng, Zhong AU - Zeng Z AD - 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, Kunming 650032, Yunnan Province, China. FAU - Wang, Kun-Hua AU - Wang KH AD - 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, Kunming 650032, Yunnan Province, China. FAU - Zhang, Hai-Yan AU - Zhang HY AD - 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, Kunming 650032, Yunnan Province, China. FAU - Wang, Shuai AU - Wang S AD - 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, Kunming 650032, Yunnan Province, China. FAU - Zhou, Wen-Xiang AU - Zhou WX AD - 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, Kunming 650032, Yunnan Province, China. FAU - Wang, Zhan-Bo AU - Wang ZB AD - 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, Kunming 650032, Yunnan Province, China. FAU - Xu, Wang-Gang AU - Xu WG AD - 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, Kunming 650032, Yunnan Province, China. FAU - Duan, Jian AU - Duan J AD - 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, Kunming 650032, Yunnan Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Enzyme Inhibitors) RN - 0 (Myd88 protein, rat) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Protoporphyrins) RN - 0 (Ticam1 protein, rat) RN - 0 (Tlr2 protein, rat) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 15442-64-5 (zinc protoporphyrin) RN - 63AAN3JDZE (cobaltiprotoporphyrin) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) SB - IM MH - Adaptor Proteins, Vesicular Transport/metabolism MH - Animals MH - Cytoprotection MH - Disease Models, Animal MH - Enzyme Inhibitors/pharmacology MH - Heme Oxygenase (Decyclizing)/antagonists & inhibitors/*metabolism MH - Liver/*drug effects/enzymology/immunology/pathology MH - Male MH - Myeloid Differentiation Factor 88/metabolism MH - Protoporphyrins/*pharmacology MH - Rats, Sprague-Dawley MH - Reperfusion Injury/enzymology/etiology/immunology/pathology/*prevention & control MH - Signal Transduction/*drug effects MH - Toll-Like Receptor 2/*drug effects/metabolism MH - Toll-Like Receptor 4/*drug effects/metabolism MH - Warm Ischemia/*adverse effects PMC - PMC4356913 OTO - NOTNLM OT - Heme oxygenase-1 OT - Ischemia reperfusion injury OT - Liver OT - Myeloid differentiation factor 88 OT - Toll-like receptor EDAT- 2015/03/18 06:00 MHDA- 2015/10/16 06:00 PMCR- 2015/03/14 CRDT- 2015/03/18 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2014/08/09 00:00 [revised] PHST- 2014/11/07 00:00 [accepted] PHST- 2015/03/18 06:00 [entrez] PHST- 2015/03/18 06:00 [pubmed] PHST- 2015/10/16 06:00 [medline] PHST- 2015/03/14 00:00 [pmc-release] AID - 10.3748/wjg.v21.i10.2937 [doi] PST - ppublish SO - World J Gastroenterol. 2015 Mar 14;21(10):2937-48. doi: 10.3748/wjg.v21.i10.2937.