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Interleukin-18 binding protein regulates the apoptosis and necroptosis of fibroblast-like synoviocytes and chondrocytes in rheumatoid arthritis
H.K. Min1, S.H. Kim2, J.-Y. Lee3, S.-H. Lee4, H.-R. Kim5
- Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.
- The Rheumatism Research Center, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea. kimhaerim@kuh.ac.kr
CER16433
2023 Vol.41, N°11
PI 2207, PF 2215
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PMID: 37083154 [PubMed]
Received: 06/12/2022
Accepted : 24/03/2023
In Press: 13/04/2023
Published: 14/11/2023
Abstract
OBJECTIVES:
Interleukin (IL)-18 plays a pro-inflammatory role in rheumatoid arthritis (RA), and its soluble inhibitor IL-18 binding protein (IL-18BP) has a potential therapeutic role. We investigated the role of IL-18BP on the joint destruction process of RA by accessing the effects of IL-18BP on fibroblast-like synoviocytes (FLSs) and chondrocytes.
METHODS:
Peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls were cultured under T cell proliferative conditions with 10, 50, or 100 ng/mL of IL-18BP. After three days of culture, flow cytometry for CD4+ T cells was performed using various IL-18BP concentrations. The apoptosis and necroptosis of FLSs and chondrocytes were measured by flow cytometry using annexin V and propidium iodide (PI) and western blot under TNF-α stimulation with IL-18BP (10, 50, and 100 ng/mL).
RESULTS:
Differentiation of CD4+ IL-17A+ and CD4+ IL-4+ cells decreased and that of CD4+ CD25high Foxp3+ and CD4+ interferon (IFN)-γ+ cells increased on addition of IL-18BP to cultured RA patient-driven PBMCs. RA-FLS migration ability was not suppressed by IL-18BP after 12 or 24 h. IL-18BP increased annexin V+ FLS level and reduced annexin V+ chondrocyte level in a dose-dependent manner, whereas PI+ annexin V- FLS and chondrocyte levels were suppressed by 50, 100 ng/mL IL-18BP in culture.
CONCLUSIONS:
The administration of IL-18BP regulated the type 17 helper T cell/ regulatory T cell imbalance and attenuated the production of pro-inflammatory cytokines. IL-18BP further increased FLS apoptosis and decreased the necroptosis of FLS/chondrocytes and apoptosis of chondrocytes suggesting the joint preservative potential of IL-18BP.
