Interleukin-18-induced inflammatory responses in synoviocytes and chondrocytes from osteoarthritic patients

Fu,Zhaozong; Liu,Peng; Yang,Dehong; Wang,Fenglong; Yuan,Liang; Lin,Zhen; Jiang,Jianming

doi:10.3892/ijmm.2012.1073

Interleukin-18-induced inflammatory responses in synoviocytes and chondrocytes from osteoarthritic patients

Authors:
- Zhaozong Fu
- Peng Liu
- Dehong Yang
- Fenglong Wang
- Liang Yuan
- Zhen Lin
- Jianming Jiang
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Affiliations: Department of Spine Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China
Published online on: July 20, 2012 https://doi.org/10.3892/ijmm.2012.1073
Pages: 805-810

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Abstract

The major pathological changes of osteoarthritis (OA) include cartilage degeneration and synovial inflammation. Previous studies confirmed that interleukin-1 (IL-1) stimulates the secretion of multiple inflammatory factors in synoviocytes and chondrocytes. IL-18 is a member of the IL-1 superfamily. In this study, the pro-inflammatory effects of IL-18 on synoviocytes and chondrocytes in patients with OA were investigated. Knee synovial membrane and cartilage samples were obtained from OA patients, then primary cells were cultured. Synoviocytes and primary chondrocytes at different generations (primary, secondary and tertiary), were stimulated with IL-18, then inflammatory marker levels, including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2), were measured using reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. IL-1 receptor antagonist (IL-1Ra) was applied to interfere with the IL-18 stimulation of chondrocytes, and then the COX-2 expression in chondrocytes and the PGE2 levels in the medium were measured. The expression of IL-18 receptor α (IL-18Rα) and IL-18 receptor β (IL-18Rβ) in synoviocytes and chondrocytes was assessed, using RT-PCR. Our results showed that IL-18 stimulated the COX-2 and TNF-α expressions in primary synoviocytes, while increasing PGE2 and TNF-α levels in the supernatant (P<0.05) of the culture medium in primary synoviocytes. IL-18 also induced high PGE2 level production in second-generation synoviocytes (P<0.05). Moreover, IL-18 upregulated COX-2 and TNF-α mRNA in chondrocytes, while promoting PGE2 and TNF-α (P<0.05) secretions in a dose-dependent manner. The induced effects were not attenuated by the addition of IL-1Ra (P<0.05). IL-18Rα was expressed in the chondrocytes and synoviocytes of 4/8 patients, while IL-18Rβ was expressed in the chondrocytes of 4/8 patients and in the synoviocytes of 2/8 patients. We conclude that IL-18 induces inflammatory responses in synoviocytes and chondrocytes and that this effect was correlated with, although not entirely dependent on, IL-1β.

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