Possible role of granulysin in pathogenesis of osteoarthritis.
Increased presence of immune mediator and cytotoxic/apoptotic molecule granulysin was noticed in different tissues during pathological processes with the domination of Th1 over Th2 mediated immunity. Beside granulysin expression in T and NKT cells, activated NK cells are thought to be the major source of chemotactic 15 kDa and cytotoxic 9 kDa granulysin in vivo. As NK cells are the principal joint's tissue-infiltrating lymphocyte subset, we hypothesized that granulysin mediated human cell death (apoptosis) could be responsible for the relatively silent damage of the joint's tissue without clinically notable signs of systemic inflammation in the patients with osteoarthritis (OA). The analyzes of the presence and frequency of granulysin expressing lymphocytes at protein and gene levels in peripheral blood and synovial samples and/or the samples of joint's tissue after the joint replacement therapy in patients with OA could give the initial insight to evaluate our hypothesis. It would be of the particular interest to differentiate the expression of 9 kDa and 15 kDa granulysin forms in the effector cells, since only the shorter form exhibits cytotoxic properties. The measurement of granulysin mediated early apoptosis in human NK sensitive K562 cells could be suitable in vitro model for evaluating granulysin activity. Furthermore, disturbed balance of pro-inflammatory and anti-inflammatory cytokines in OA patients, could influence the level of the granulysin expression. Having in mind that the granulysin and its regulation is still unknown in the pathogenesis of OA, it could be worth to explore this important pro-inflammatory, cytotoxic/apoptotic mediator.
Department of Rheumatology, Rehabilitation and Physical Medicine, Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia; Department of Medical Rehabilitation, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: tatjana.kehler@ri.T-com.hr.
Tatjana
T
Kehler
Department of Rheumatology, Rehabilitation and Physical Medicine, Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia; Department of Physiology and Immunology, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: gordana.laskarin@medri.uniri.hr.
Gordana
G
Laskarin
Department of Rheumatology, Rehabilitation and Physical Medicine, Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia; Department of Medical Rehabilitation, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: drazen.massari@tto.hr.
Drazen
D
Massari
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: marin.dominovic@gmail.com.
Marin
M
Dominovic
Department of Medical Rehabilitation, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia; Division of Cardiology, Hospital for Medical Rehabilitation of the Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia. Electronic address: viktor.persic@ri.T-com.hr.
Viktor
V
Persic
Division of Cardiology, Hospital for Medical Rehabilitation of the Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia. Electronic address: ivan_rosovic@yahoo.com.
Ivan
I
Rosovic
Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism "Thalassotherapia-Opatija", M. Tita 188, 51410 Opatija, Croatia. Electronic address: josip.laginja@ri.T-com.hr.
Josip
J
Laginja
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia; Department of Clinical and Transplantation Immunology and Molecular Medicine in Rijeka, Croatian Academy of Sciences and Arts, Radmile Matejcic 2, Rijeka, Croatia. Electronic address: daniel@medri.uniri.hr.
Daniel
D
Rukavina
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017209:Apoptosis; D002356:Cartilage / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007111:Immunity, Cellular; D007249:Inflammation; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology; D010003:Osteoarthritis / Q000503:physiopathology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C075005:GNLY protein, human