The Eurasian Journal of Medicine
Original Article

Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis


Department of Medical Biology and Genetics, İnönü University Faculty of Medicine, Malatya, Turkey


Department of Histology and Embryology İnönü University Faculty of Medicine, Malatya, Turkey


Transplantation Immunology Laboratory, Department of General Surgery, Liver Transplantation Institute, İnönü University, Malatya, Turkey


Department of Pharmaceutical Microbiology, Anadolu University Faculty of Pharmacy, Eskişehir, Turkey

Eurasian J Med 2022; 54: 27-35
DOI: 10.5152/eurasianjmed.2022.20030
Read: 362 Downloads: 114 Published: 01 February 2022

Objective: Lipoxins are anti-inflammatory, pro-resolving molecules that are secreted by immune cells such as neutrophils and macrophages. Lipoxins are a metabolite of the arachidonic acid pathway that resolve inflammation in fibrotic liver by producing several anti-inflammatory molecules. In this study, phenotypic distribution activation markers of lymphocytes in the spleen and expression levels of chemokines (chemokine (C-X-C motif) receptor 3, chemokine (C-X-C motif) ligand 10) cytokines (interferon gamma, tumor necrosis factor alpha, interleukin-6, interleukin-10) in the liver of lipoxin A4-treated fibrotic mice were investigated.

Materials and methods: Liver fibrosis was induced in BALB/c mice by thioacetamide administration. Lipoxin A4 was administered during last 2 weeks of induction. Fibrosis level was determined by using Knodell scoring. Lymphocytes were identified by flow-cytometry. Expression levels of genes were measured by quantitative real time polymerase chain reaction in liver homogenates.

Results: Lipoxin A4 treatment caused an elevation of T-lymphocyte percentage in the spleen. Interestingly, administration of lipoxin A4 significantly reduced B-lymphocyte population in spleen of fibrotic group. CD8+ cytotoxic T cell frequency significantly reduced in thioacetamide-induced mice; however, lipoxin A4 administration increased that percentage significantly. Lipoxin A4 treatment significantly reduced frequency of activated (CD8+CD69+) cytotoxic T cells. Expression levels of chemokines significantly reduced in the liver after lipoxin A4 treatment. While expression levels of interferon gamma, tumor necrosis factor alpha, and interleukin-6 significantly reduced in the liver after lipoxin A4 treatment, an anti-inflammatory cytokine interleukin-10 expression was almost at similar levels in all experimental groups.

Conclusion: Lipoxin A4 performs its anti-inflammatory effect by reducing the frequency of activated T cells and expression levels of chemokines cytokines responsible from inflammatory immune response in the liver.

Cite this article as: Mete Karaca Z, Latife Kurtoğlu E, Gül M, Kayhan B. Influence of lipoxin-A4 treatment on cytokine, chemokine genes expression, and phenotypic distribution of lymphocyte subsets during experimental liver fibrosis. Eurasian J Med 2022;54(1):27-35.

EISSN 1308-8742