Interferon-gamma inhibits interleukin-1 beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis

Page, Charlotte E., Smale, Shaun, Carty, Sara Madelaine, Amos, Nick, Lauder, Sarah Nicol, Goodfellow, Rhian Mair, Richards, Peter J., Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711, Topley, Nicholas and Williams, Anwen Sian ORCID: https://orcid.org/0000-0001-6118-020X 2010. Interferon-gamma inhibits interleukin-1 beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis. Arthritis Research and Therapy 12 (2) , R49.

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Abstract

Introduction: The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-γ (IFN-γ) during early inflammatory arthritis. Methods: We studied IFN-γ's capacity to modulate interleukin-1β (IL-1β) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)). Results: IFN-γ modulated IL-1β driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-γ did not affect IL-1β induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-γ reduced IL-1β expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. Conclusions: Early therapeutic intervention with IFN-γ may be critical to orchestrate tissue-protective responses during inflammatory arthritis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1478-6354/ (accessed 25/02/2014)
Publisher:	BioMed Central
ISSN:	1478-6354
Date of First Compliant Deposit:	30 March 2016
Last Modified:	09 Aug 2024 13:53
URI:	https://orca.cardiff.ac.uk/id/eprint/43493

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