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

Autor: Drvar V; Clinical Department of Laboratory Diagnostics, University Hospital Centre Rijeka, 51000 Rijeka, Croatia., Ćurko-Cofek B; Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia., Karleuša L; Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia., Aralica M; Clinical Department of Laboratory Diagnostics, University Hospital Centre Rijeka, 51000 Rijeka, Croatia., Rogoznica M; Hospital for Medical Rehabilitation of Health and Lung Diseases and Rheumatism 'Thalassotherapia-Opatija', 51410 Opatija, Croatia., Kehler T; Hospital for Medical Rehabilitation of Health and Lung Diseases and Rheumatism 'Thalassotherapia-Opatija', 51410 Opatija, Croatia.; Department of Medical Rehabilitation, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia., Legović D; Clinic for Orthopaedic Surgery Lovran, 51415 Lovran, Croatia., Rukavina D; Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.; Department of Biomedical Sciences in Rijeka, Croatian Academy of Sciences and Arts, 51000 Rijeka, Croatia., Laskarin G; 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.
Jazyk: angličtina
Zdroj: Biomedical reports [Biomed Rep] 2022 May; Vol. 16 (5), pp. 44. Date of Electronic Publication: 2022 Mar 24.
DOI: 10.3892/br.2022.1527
Abstrakt: 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.
Competing Interests: The authors declare that they have no competing interests.
(Copyright: © Drvar et al.)
Databáze: MEDLINE
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