Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis
Yıl: 2022 Cilt: 54 Sayı: 1 Sayfa Aralığı: 27 - 35 Metin Dili: İngilizce DOI: 10.5152/eurasianjmed.2022.20030 İndeks Tarihi: 24-06-2022
Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis
Öz: 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.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Henderson NC, Iredale JP. Liver fibrosis: cellular mechanism of progression and resolution. Clin Sci (Lond). 2007;112(5):265-280. [CrossRef]
- 2. Parsons CJ, Takashima M, Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol. 2007;22(suppl 1):S79-S84. [CrossRef]
- 3. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115(2):209-218. [CrossRef]
- 4. Satapathy SK, Sakhuja P, Malhotra V, Sharma BC, Sarin SK. Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2007;22(5):634-638. [CrossRef]
- 5. Yamaguchi N, Mezaki Y, Miura M, et al. Antiproliferative and proapoptotic effects of tocopherol and tocol on activated hepatic stellate cells. J Nutr Sci Vitaminol (Tokyo). 2011;57(5):317-325. [CrossRef]
- 6. Ahmad A, Ahmad R. Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches. Saudi J Gastroenterol. 2012;18(3):155- 167. [CrossRef]
- 7. Schwab JM, Serhan CN. Lipoxins and new lipid mediators in the resolution of inflammation. Curr Opin Pharmacol. 2006;6(4):414-420. [CrossRef]
- 8. Serhan CN, Fahlstadius P, Dahlén SE, Hamberg M, Samuelsson B. Biosynthesis and biological activities of lipoxins. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:163-166.
- 9. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005;6(12):1191-1197. [CrossRef]
- 10. Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S. Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8 and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol. 2000;164(5):2660-2666. [CrossRef]
- 11. Gewirtz AT, McCormick B, Neish AS, et al. Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A4 analogs. J Clin Invest. 1998;101(9):1860-1869. [CrossRef]
- 12. Kurtoğlu EL, Kayhan B, Gül M, et al. A bioactive product lipoxin A4 attenuates liver fibrosis in an experimental model by regulating immune response and modulating the expression of regeneration genes. Turk J Gastroenterol. 2019;30(8):745-757. [CrossRef]
- 13. Kurtoğlu EL. Karaciğer Fibrozunun Tedavisinde Lipoksin A4 Kullanımı. İ.Ü. Sağlık Bilimleri Enstitsü Doktora Tezi. 2016.
- 14. Xu Z, Zhao F, Lin F, Chen J, Huang Y. Lipoxin A4 inhibits the development of endometriosis in mice: the role of anti-inflammation and antiangiogenesis. Am J Reprod Immunol. 2012;67(6):491-497. [CrossRef]
- 15. Huang WC, Shen JJ, Liou CJ, et al. Enhancing Th1 cell activities in mice by short-term oral administration of Gynostemma pentaphyllum extracts. Bio Formosa. 2007;42:9-16.
- 16. Kaneko JJ. Normal blood analyte values in small and some laboratory animals. In: Kaneko JJ, ed. Clinical Biochemistry of Domestic Animals. San Diego, CA: Academic Press; 1989:892-898.
- 17. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598-607. [CrossRef]
- 18. Kayhan B, Yager EJ, Lanzer K, et al. A replicationdeficient murine γ-herpesvirus blocked in late viral gene expression can establish latency and elicit protective cellular immunity. J Immunol. 2007;179(12):8392-8402. [CrossRef]
- 19. Karaca G, Karaca ZM, Kayhan B, et al. The relationship between caspase-1 related inflammasomes expression and serum inflammatory cytokine levels during acute brucellosis. North Clin Istanb. 2019;6(2):117-123. [CrossRef]
- 20. Yasar S, Arslan AK, IAY ÇC. Statistical Analysis Software [web-based software]; 2019. Available at: http://biostatapps.inonu.edu.tr/IAY/.
- 21. Chandrasekharan JA, Sharma-Walia N. Lipoxins: nature’s way to resolve inflammation. Jinflammres. 2015;8:181-192. [CrossRef]
- 22. Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest. 2005;115(11):3072-3082. [CrossRef]
- 23. Canpolat E, Karaca M, Kayhan B, Kayhan B, Bayındır Y, Yılmaz S. Attenuation of antibody response and elevation of CD4+CD25+Foxp3+ Treg cell frequency during chronic liver fibrosis. Hepatology. (Supplement of 68th Annual Meeting of the American Association for the Study of Liver Diseases). 2017;66:687A.
- 24. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 2011;25(2):195-206. [CrossRef]
- 25. Pellicoro A, Ramachandran P, Iredale JP, Fallowfield JA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol. 2014;14(3):181-194. [CrossRef]
- 26. Muhanna N, Horani A, Doron S, Safadi R. Lymphocyte–hepatic stellate cell proximity suggests a direct interaction. Clin Exp Immunol. 2007;148(2):338-347. [CrossRef]
- 27. Marra F, Tacke F. Roles of chemokines in liver disease. Gastroenterology. 2014;147(3):577-594. e1. [CrossRef]
- 28. Groom JR, Luster AD. CXCR3 in T cell function. Exp Cell Res. 2011;317(5):620-631. [CrossRef]
- 29. Hintermann E, Bayer M, Pfeilschifter JM, Luster AD, Christen U. CXCL10 promotes liver fibrosis by prevention of NK cell mediated hepatic stellate cell inactivation. J Autoimmun. 2010;35(4):424-435. [CrossRef]
- 30. Machado FS, Johndrow JE, Esper L, et al. Antiinflammatory actions of lipoxin A4 and aspirintriggered lipoxin are SOCS-2 dependent. Nat Med. 2006;12(3):330-334. [CrossRef]
| APA | karaca z, Aslan E, GÜL M, KAYHAN B (2022). Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. , 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| Chicago | karaca zeynal mete,Aslan Elçin Latife,GÜL MEHMET,KAYHAN Başak Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. (2022): 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| MLA | karaca zeynal mete,Aslan Elçin Latife,GÜL MEHMET,KAYHAN Başak Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. , 2022, ss.27 - 35. 10.5152/eurasianjmed.2022.20030 |
| AMA | karaca z,Aslan 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. . 2022; 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| Vancouver | karaca z,Aslan 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. . 2022; 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| IEEE | karaca z,Aslan 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." , ss.27 - 35, 2022. 10.5152/eurasianjmed.2022.20030 |
| ISNAD | karaca, zeynal mete vd. "Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis". (2022), 27-35. https://doi.org/10.5152/eurasianjmed.2022.20030 |
| APA | karaca z, Aslan E, GÜL M, KAYHAN B (2022). Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. Eurasian Journal of Medicine, 54(1), 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| Chicago | karaca zeynal mete,Aslan Elçin Latife,GÜL MEHMET,KAYHAN Başak Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. Eurasian Journal of Medicine 54, no.1 (2022): 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| MLA | karaca zeynal mete,Aslan Elçin Latife,GÜL MEHMET,KAYHAN Başak Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis. Eurasian Journal of Medicine, vol.54, no.1, 2022, ss.27 - 35. 10.5152/eurasianjmed.2022.20030 |
| AMA | karaca z,Aslan 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 Journal of Medicine. 2022; 54(1): 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| Vancouver | karaca z,Aslan 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 Journal of Medicine. 2022; 54(1): 27 - 35. 10.5152/eurasianjmed.2022.20030 |
| IEEE | karaca z,Aslan 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 Journal of Medicine, 54, ss.27 - 35, 2022. 10.5152/eurasianjmed.2022.20030 |
| ISNAD | karaca, zeynal mete vd. "Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis". Eurasian Journal of Medicine 54/1 (2022), 27-35. https://doi.org/10.5152/eurasianjmed.2022.20030 |
