title: Treatment with Recombinant Trichinella spiralis Cathepsin B-like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages.
abstract: Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B-like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2-M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; and.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
authors.forename: Jian-Tong
authors.initials: JT
authors.lastname: Shen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou 510080, China.
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; liukexuan705@163.com.
authors.forename: Ke-Xuan
authors.initials: KX
authors.lastname: Liu
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001119:Arginase / Q000235:genetics / Q000276:immunology; D002401:Cathepsin B / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000145:classification / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D011743:Pyrimidines / Q000494:pharmacology; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D016019:Survival Analysis; D017160:Trichinella spiralis / Q000737:chemistry / Q000276:immunology; D014611:Vaccination
chemical_list: C544923:4-(benzylamino)-2-((2-(3-chloro-4-hydroxyphenyl)ethyl)amino)pyrimidine-5-carboxamide; D000947:Antigens, Helminth; C515371:Ccr7 protein, mouse; D011743:Pyrimidines; D054400:Receptors, CCR7; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D002401:Cathepsin B; C544448:Arg1 protein, mouse; D001119:Arginase