PMID- 37137833 OWN - NLM STAT- MEDLINE DCOM- 20230505 LR - 20230505 IS - 1007-3418 (Print) IS - 1007-3418 (Linking) VI - 31 IP - 2 DP - 2023 Feb 20 TI - [Roles of the CXCR1/CXCL8 axis in abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis]. PG - 174-180 LID - 10.3760/cma.j.cn501113-20210726-00362 [doi] AB - Objective: To investigate the role of the CXC chemokine receptor 1 (CXCR1)/CXC chemokine ligand 8 (CXCL8) axis in the abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis (PBC). Methods: 30 female C57BL/6 mice were randomly divided into the PBC model group (PBC group), reparixin intervention group (Rep group), and blank control group (Con group) in an in vivo experiment. PBC animal models were established after 12 weeks of intraperitoneal injection of 2-octanoic acid coupled to bovine serum albumin (2OA-BSA) combined with polyinosinic acid polycytidylic acid (polyI:C). After successful modelling, reparixin was injected subcutaneously into the Rep group (2.5 mg . kg(-1) . d(-1), 3 weeks). Hematoxylin-eosin staining was used to detect histological changes in the liver. An immunohistochemical method was used to detect the expression of cytokeratin 19 (CK-19). Tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (IFN-gamma) and interleukin (IL)-6 mRNA expression were detected by qRT-PCR. Western blot was used to detect nuclear transcription factor-kappaB p65 (NF-kappaB p65), extracellularly regulated protein kinase 1/2 (ERK1/2), phosphorylated extracellularly regulated protein kinase 1/2 (p-ERK1/2), Bcl-2-related X protein (Bax), B lymphoma-2 (Bcl-2), and cysteine proteinase-3 (Caspase- 3) expression. Human intrahepatic bile duct epithelial cells were divided into an IL-8 intervention group (IL-8 group), an IL-8+Reparicin intervention group (Rep group), and a blank control group (Con group) in an in vitro experiment. The IL-8 group was cultured with 10 ng/ml human recombinant IL-8 protein, and the Rep group was cultured with 10 ng/ml human recombinant IL-8 protein, followed by 100 nmol/L Reparicin. Cell proliferation was detected by the EdU method. The expression of TNF-alpha, IFN-gamma and IL-6 was detected by an enzyme-linked immunosorbent assay. The expression of CXCR1 mRNA was detected by qRT-PCR. The expression of NF-kappaB p65, ERK1/2 and p-ERK1/2 was detected by western blot. A one-way ANOVA was used for comparisons between data sets. Results: The results of in vivo experiments revealed that the proliferation of cholangiocytes, the expression of NF-kappaB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the Con group compared with the PBC group. However, reparixin intervention reversed the aforementioned outcomes (P<0.05). In vitro experiments showed that the proliferation of human intrahepatic cholangiocyte epithelial cells, the expression of CXCR1 mRNA, the expression of NF-kappaB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the IL-8 group compared with the Con group. Compared with the IL-8 group, the proliferation of human intrahepatic cholangiocyte epithelial cells, NF-kappaB and ERK pathway-related proteins, and inflammatory indicators were significantly reduced in the Rep group (P < 0.05). Conclusion: The CXCR1/CXCL8 axis can regulate the abnormal proliferation of bile duct epithelial cells in PBC, and its mechanism of action may be related to NF-kappaB and ERK pathways. FAU - Ai, X AU - Ai X AD - Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. FAU - Fu, H Y AU - Fu HY AD - Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. FAU - Xu, J M AU - Xu JM AD - Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. FAU - Yang, W X AU - Yang WX AD - Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. FAU - Tang, Y M AU - Tang YM AD - Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. LA - chi GR - 81660102/National Natural Science Foundation of China/ GR - 2018FE001 (-051)/Natural Science Foundation of Yunnan Province/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Gan Zang Bing Za Zhi JT - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JID - 9710009 RN - U604E1NB3K (reparixin) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Receptors, Interleukin-8A) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 82115-62-6 (Interferon-gamma) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - EC 2.7.- (Protein Kinases) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Mice MH - Female MH - Humans MH - *Interleukin-8/metabolism MH - NF-kappa B/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Receptors, Interleukin-8A/metabolism MH - *Liver Cirrhosis, Biliary/pathology MH - Mice, Inbred C57BL MH - Cytokines/metabolism MH - Bile Ducts/pathology MH - Interleukin-6 MH - Epithelial Cells/metabolism/pathology MH - Interferon-gamma/metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Protein Kinases/metabolism MH - RNA, Messenger/metabolism OTO - NOTNLM OT - Biliary epithelial cells OT - CXCL8 OT - CXCR1 OT - Primary biliary cholangitis OT - Proliferation EDAT- 2023/05/04 00:42 MHDA- 2023/05/05 06:42 CRDT- 2023/05/03 22:49 PHST- 2023/05/05 06:42 [medline] PHST- 2023/05/04 00:42 [pubmed] PHST- 2023/05/03 22:49 [entrez] AID - 10.3760/cma.j.cn501113-20210726-00362 [doi] PST - ppublish SO - Zhonghua Gan Zang Bing Za Zhi. 2023 Feb 20;31(2):174-180. doi: 10.3760/cma.j.cn501113-20210726-00362.