PMID- 33276196 OWN - NLM STAT- MEDLINE DCOM- 20210607 LR - 20240226 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 90 DP - 2021 Jan TI - Apolipoprotein A4 regulates the immune response in carbon tetrachloride-induced chronic liver injury in mice. PG - 107222 LID - S1567-5769(20)33689-4 [pii] LID - 10.1016/j.intimp.2020.107222 [doi] AB - This article explores the role of ApoA4 in a CCl(4)-induced chronic liver injury (CLI) mouse model. C57BL/6J mice (WT) and ApoA4 knock-out (KO) mice were divided into CCl(4) CLI (WT-CCl(4) and KO-CCl(4)) and olive oil solvent control groups (WT-Veh and KO-Veh). Some of the KO-CCl(4) mice were additionally treated with recombinant mouse ApoA4 and primary mouse T lymphocyte injections. After 6 weeks, histological analyses, biochemical and superoxide dismutase (SOD) and malondialdehyde (MDA) assays, flow cytometry of immune cells and qRT-PCR analyses were performed. KO mice after treatment with CCl(4) showed reduced hepatic SOD and enhanced serum MDA activities leading to worsening liver injury and fibrosis compared with WT-CCl(4), accompanied by enhanced hepatic alpha smooth muscle actin (alpha-SMA), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen type I alpha 1 chain (COL1A1) transcriptions, elevated macrophage M1 levels, enhanced tumor necrosis factor-alpha (TNF-alpha), Interleukin 6 (IL-6) and C-C Motif Chemokine Ligand 5 (CCL5), but reduced Interleukin 10 (IL-10), monocyte chemotactic protein 1 (MCP-1), C-C Motif Chemokine Receptor 2 (CCR2), C-X3-C Motif Chemokine Receptor 1 (CX3CR1) and C-X-C Motif Chemokine Ligand 9 (CXCL9) transcription, as well as reduced CD3+, CD4+ and CD8+ T cell percentages in hepatic tissue, blood cells and spleen. In addition, CD11b+CD115+, CD11b+/Ly6C(high), CD11b+/LyC6(-) and CD11b+/Ly6C(int) cells were enhanced, which partly reversed by ApoA4 protein and T cell injections. In conclusion, we propose that ApoA4 might be involved in liver protection via inhibiting fibrotic mediators and inflammatory cytokines, suppression of pro-inflammatory hepatic M1 cell invasion and regulation of CD8+ T and CD4+ T lymphocytes. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Wang, Yinan AU - Wang Y AD - Bio-evidence Science Academy (BSA), Xi'an Jiaotong University (XJTU), No. 205 Zhuque Street, Xi'an 710061, China; Key laboratory of Ministry of Public Health for Forensic Sciences, No. 205 Zhuque Street, Xi'an 710061, China. FAU - Yang, Ziyu AU - Yang Z AD - Bio-evidence Science Academy (BSA), Xi'an Jiaotong University (XJTU), No. 205 Zhuque Street, Xi'an 710061, China; Key laboratory of Ministry of Public Health for Forensic Sciences, No. 205 Zhuque Street, Xi'an 710061, China. FAU - Wei, Yang AU - Wei Y AD - National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Precision Medical Institute, Institute of Digestive Diseases. The Second Affiliated Hospital, Xi'an Jiaotong University, No. 157 West 5th Road, Xi'an 710004, China. FAU - Li, Xiaoming AU - Li X AD - National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Precision Medical Institute, Institute of Digestive Diseases. The Second Affiliated Hospital, Xi'an Jiaotong University, No. 157 West 5th Road, Xi'an 710004, China. Electronic address: lixiaoming022916@163.com. FAU - Li, Shengbin AU - Li S AD - Bio-evidence Science Academy (BSA), Xi'an Jiaotong University (XJTU), No. 205 Zhuque Street, Xi'an 710061, China; Key laboratory of Ministry of Public Health for Forensic Sciences, No. 205 Zhuque Street, Xi'an 710061, China. Electronic address: shengbin_li19@163.com. LA - eng PT - Journal Article DEP - 20201201 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Apolipoproteins A) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (apolipoprotein A-IV) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Adoptive Transfer MH - Animals MH - Apolipoproteins A/genetics/*metabolism MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Carbon Tetrachloride MH - Chemical and Drug Induced Liver Injury, Chronic/immunology/*metabolism/pathology MH - Chemotaxis, Leukocyte MH - Cytokines/genetics/*metabolism MH - Gene Expression Regulation MH - Inflammation Mediators/*metabolism MH - Liver/immunology/metabolism/pathology MH - Liver Cirrhosis/chemically induced/immunology/*metabolism/pathology MH - Macrophages/immunology/metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Oxidative Stress MH - Phenotype MH - Signal Transduction MH - Mice OTO - NOTNLM OT - Anti-fibrosis OT - Anti-inflammatory effect OT - Anti-oxidative effect OT - ApoA4 OT - CCl(4)-induced chronic liver injury (CLI) mouse model OT - Cytokines EDAT- 2020/12/05 06:00 MHDA- 2021/06/08 06:00 CRDT- 2020/12/04 20:09 PHST- 2020/06/24 00:00 [received] PHST- 2020/11/02 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/12/05 06:00 [pubmed] PHST- 2021/06/08 06:00 [medline] PHST- 2020/12/04 20:09 [entrez] AID - S1567-5769(20)33689-4 [pii] AID - 10.1016/j.intimp.2020.107222 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Jan;90:107222. doi: 10.1016/j.intimp.2020.107222. Epub 2020 Dec 1.