Fulltext:
173999.pdf
Embargo:
until further notice
Size:
575.6Kb
Format:
PDF
Description:
Publisher’s version
Publication year
2017Source
Rheumatology, 56, 3, (2017), pp. 351-361ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Rheumatology
Orthopaedics
Journal title
Rheumatology
Volume
vol. 56
Issue
iss. 3
Page start
p. 351
Page end
p. 361
Subject
Radboudumc 10: Reconstructive and regenerative medicine RIHS: Radboud Institute for Health Sciences; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences; Orthopaedics Radboud University Medical Center; Rheumatology Radboud University Medical CenterAbstract
Objective.: A crucial feature of OA is cartilage degradation. This process is mediated by pro-inflammatory cytokines, among other factors, via induction of matrix-degrading enzymes. Interleukin 37 (IL37) is an anti-inflammatory cytokine and is efficient in blocking the production of pro-inflammatory cytokines during innate immune responses. We hypothesize that IL37 is therapeutic in treating the inflammatory cytokine cascade in human OA chondrocytes and can act as a counter-regulatory cytokine to reduce cartilage degradation in OA. Methods.: Human OA cartilage was obtained from patients undergoing total knee or hip arthroplasty. Immunohistochemistry was applied to study IL37 protein expression in cartilage biopsies from OA patients. Induction of IL37 expression by IL1beta, OA synovium-conditioned medium and TNFalpha was investigated in human OA chondrocytes. Adenoviral overexpression of IL37 followed by IL1beta stimulation was performed to investigate the anti-inflammatory potential of IL37. Results.: IL37 expression was detected in cartilage biopsies of OA patients and induced by IL1beta. After IL1beta stimulation, increased IL1beta, IL6 and IL8 expression was observed in OA chondrocytes. Elevated IL37 levels diminished the IL1beta-induced IL1beta , IL6 and IL8 gene levels and IL1beta and IL8 protein levels. In addition to the reduction in pro-inflammatory cytokine expression, IL37 reduced MMP1 , MMP3 , MMP13 and disintegrin and metalloproteinase with thrombospondin motifs 5 gene levels and MMP3 and MMP13 protein levels. Conclusion.: IL37 is induced by IL1beta, and IL37 itself reduced IL1beta, IL6 and IL8 production, indicating that IL37 is able to induce a counter-regulatory anti-inflammatory feedback loop in chondrocytes. In addition, IL37 dampens catabolic enzyme expression. This supports IL37 as a potential therapeutic target in OA.
This item appears in the following Collection(s)
- Academic publications [245050]
- Electronic publications [132309]
- Faculty of Medical Sciences [93209]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.