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Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients

  • Authors:
    • Vedrana Drvar
    • Božena Ćurko‑Cofek
    • Ljerka Karleuša
    • Merica Aralica
    • Marija Rogoznica
    • Tatjana Kehler
    • Dalen Legović
    • Daniel Rukavina
    • Gordana Laskarin
  • View Affiliations / Copyright

    Affiliations: Clinical Department of Laboratory Diagnostics, University Hospital Centre Rijeka, 51000 Rijeka, Croatia, Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia, Hospital for Medical Rehabilitation of Health and Lung Diseases and Rheumatism ‘Thalassotherapia‑Opatija’, 51410 Opatija, Croatia, Clinic for Orthopaedic Surgery Lovran, 51415 Lovran, Croatia
    Copyright: © Drvar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 44
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    Published online on: March 24, 2022
       https://doi.org/10.3892/br.2022.1527
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Abstract

Osteoarthritis (OA) is a chronic joint disease caused by mechanical damage and metabolic factors that support the development of low‑grade inflammation. Increased levels of T helper 1 pro‑inflammatory cytokines in the serum of OA patients may support granulysin (GNLY) mediated cytotoxicity, which in‑turn may contribute to the pathogenesis of OA. In the present study, GNLY expression and cytotoxic/apoptotic mechanisms mediated by GNLY in the peripheral blood of OA patients were assessed. A total of 40 non‑obese women (median age of 64 years old) with knee OA, and 40 controls (median age 62 years old) were enrolled in the study. GNLY, IFN‑γ and IL‑4 expression levels were investigated in peripheral blood lymphocytes (PBLs) using flow cytometry, immunocytochemistry and/or confocal microscopy. Natural killer (NK) GNLY‑mediated apoptosis through NK effectors against K‑562 targets was analyzed using the PKH‑26 18‑h cytotoxicity assay. Serum GNLY levels were assessed using ELISA. The percentage of GNLY+PBLs was higher in the OA patients than that in the controls due to the increase in the proportions of GNLY+ cells in the natural killer (NK), T and natural killer T (NKT) subsets. GNLY localization inside exocytotic lysosomal‑associated membrane protein‑1+ granules was ~40% in both groups. However, the intensity of GNLY labeling in PBLs was higher in OA patients than in the controls, and it was supported by the increased expression of IFN‑γ relative to IL‑4 in NK and T cells from OA patients. The serum GNLY concentration was <0.3 ng/ml in both groups. RC8 anti‑GNLY mAb by itself was unable to significantly alter early apoptosis, whereas RC8 anti‑GNLY mAb combined with anti‑perforin mAb significantly reduced NK‑mediated early apoptosis of K‑562 targets in the OA patients, whilst not exerting a notable effect in the controls. Anti‑perforin mAb by itself did not affect apoptosis significantly. These results suggest that in women with knee OA, GNLY expression in the PBL subsets and GNLY‑mediated early apoptosis of K‑562 targets are increased compared with the controls and accompanied by intracellular dominance of IFN‑γ over IL‑4 in NK cells.
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Copy and paste a formatted citation
Spandidos Publications style
Drvar V, Ćurko‑Cofek B, Karleuša L, Aralica M, Rogoznica M, Kehler T, Legović D, Rukavina D and Laskarin G: Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients. Biomed Rep 16: 44, 2022.
APA
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T. ... Laskarin, G. (2022). Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients. Biomedical Reports, 16, 44. https://doi.org/10.3892/br.2022.1527
MLA
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T., Legović, D., Rukavina, D., Laskarin, G."Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients". Biomedical Reports 16.5 (2022): 44.
Chicago
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T., Legović, D., Rukavina, D., Laskarin, G."Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients". Biomedical Reports 16, no. 5 (2022): 44. https://doi.org/10.3892/br.2022.1527
Copy and paste a formatted citation
x
Spandidos Publications style
Drvar V, Ćurko‑Cofek B, Karleuša L, Aralica M, Rogoznica M, Kehler T, Legović D, Rukavina D and Laskarin G: Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients. Biomed Rep 16: 44, 2022.
APA
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T. ... Laskarin, G. (2022). Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients. Biomedical Reports, 16, 44. https://doi.org/10.3892/br.2022.1527
MLA
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T., Legović, D., Rukavina, D., Laskarin, G."Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients". Biomedical Reports 16.5 (2022): 44.
Chicago
Drvar, V., Ćurko‑Cofek, B., Karleuša, L., Aralica, M., Rogoznica, M., Kehler, T., Legović, D., Rukavina, D., Laskarin, G."Granulysin expression and granulysin‑mediated apoptosis in the peripheral blood of osteoarthritis patients". Biomedical Reports 16, no. 5 (2022): 44. https://doi.org/10.3892/br.2022.1527
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