PANCREATIC IMMUNE CELL ALTERATIONS IN AN ANIMAL MICE MODEL OF LIVER FIBROSIS
| dc.contributor.author | Diana Abu Arra | |
| dc.date.accessioned | 2024-05-26T07:39:15Z | |
| dc.date.available | 2024-05-26T07:39:15Z | |
| dc.date.issued | 2023-10-19 | |
| dc.description.abstract | Abstract Background: Liver fibrosis is closely linked to the most common metabolic illnesses and developing acute pancreatitis (AP). Aims: This study aims to investigate the effects of liver fibrosis on modulating changes in pancreatic NK cells and involvement of molecular pathways in a mice model of liver injury. Methodology: Carbon-tetrachloride; CCl4 (i.p injected) of acute (2 weeks) and chronic (4 weeks) models of male C57/BL mice of liver injury was performed. At the end of experiments, mice were anaesthetized, and serum was collected for assessing liver enzymes, pancreatic injury of lipase and amylase. Annexin V examination of the pancreatic tissue for β-islet cell apoptosis, metabolic makers of C-peptide levels as well as for lipid and glucose profiles were performed. The livers were harvested for histological evaluations of inflammatory (H&E staining) and fibrotic (Sirius Red stain) profiles. Moreover, real-time polymerase chain reaction (PCR) was used for SMA and collagen III. IL-6 levels from pancreatic β-Islet cells were also evaluated. Pancreatic tissue-resident (tr)NK cells were isolated and evaluated for their activity through assessing INF- γ and IL-6 receptor by the ELISA. Results: In the chronic CCl4 induced-model histological characterization of the liver injury was deteriorated as compared to the acute model and the naïve mice. Serum ALT and AST levels, as well as metabolic evaluations of cholesterol, triglyceride, C-peptide, fasting blood sugar, and fibrotic profiles revealed a positive relationship with illness progression and severity of liver fibrosis. Pancreatic enzymes were elevated in liver fibrosis mice model and were associated with β-islet cells apoptosis. An inverse strength association between IL-6 of β-Islet cells and severities of liver fibrosis was achieved. β-Islet cells which exhibit high secretions to IL6 and caused an up-expressions of trNK IL6R, which in part, affected trNK activity and caused their inability to produce enough quantities of IFN-γ. Conclusion: Liver fibrosis induces pancreatic injury, as evidenced by elevated amylase and lipase levels and increased islet cell apoptosis. Dysregulation of lipid and glucose metabolism might have implications for pancreatic health. Antagonizing IL6 and/or IL6R could improve NK cell activity and delay progression of AP. Keywords: Pancreas; NK cells; liver fibrosis; mice model . | |
| dc.identifier.uri | https://hdl.handle.net/20.500.11888/18863 | |
| dc.language.iso | en | |
| dc.supervisor | Dr. Johnny Amer | |
| dc.title | PANCREATIC IMMUNE CELL ALTERATIONS IN AN ANIMAL MICE MODEL OF LIVER FIBROSIS | |
| dc.type | Thesis |