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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Jan 2004; 63(1): 43–49.
PMCID: PMC1754734

Interferon ß stimulates interleukin 1 receptor antagonist production in human articular chondrocytes and synovial fibroblasts

Abstract

Background: Interferon (IFN) ß displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however.

Objective: To investigate the effects of IFNß on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts.

Methods: Chondrocytes and synovial fibroblasts were stimulated with IFNß alone or in combination with interleukin (IL) 1ß. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction.

Results: In chondrocytes, IFNß alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1ß. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1ß and IFNß. Consistently, IL1ß and IFNß induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNß alone dose dependently increased IL1Ra secretion. In addition, IFNß enhanced the stimulatory effect of IL1ß on IL1Ra production. In synovial cell lysates, IFNß and IL1ß also increased IL1Ra levels. Consistently, IFNß and IL1ß induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts.

Conclusion: IFNß increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.

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Selected References

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Figures and Tables

Figure 1
Expression of IFNAR1 and IFNAR2 mRNA in human articular chondrocytes and synovial fibroblasts. Expression of mRNA encoding (A) IFNAR1 and (B) IFNAR2 was assessed by RT-PCR using total RNA from freshly isolated (lanes 1, 6, 7) or dedifferentiated (passage ...
Figure 2
Dose dependent effects of IFNß and IL1ß on IL1Ra secretion by human articular chondrocytes. (A) Human articular chondrocytes freshly isolated from OA knee joint cartilage or (B) dedifferentiated human articular chondrocytes (passage 4, ...
Figure 3
Effects of IFNß and IL1ß on the production of secreted and intracellular IL1Ra by in human articular chondrocytes. (A) Human articular chondrocytes freshly isolated from normal adult femoral head cartilage or (B) dedifferentiated human ...
Figure 4
Effects of IFNß and IL1ß on the expression of sIL1Ra mRNA in human articular chondrocytes. Expression of mRNA encoding sIL1Ra was quantified by real time RT-PCR using total RNA from dedifferentiated human articular chondrocytes (passages ...
Figure 5
Dose dependent effects of IFNß and IL1ß on IL1Ra production in human synovial fibroblasts. (A) Human OA synovial fibroblasts (passage 4) were left unstimulated (control; white bars) or stimulated with indicated doses of IFNß (grey ...
Figure 6
Effects of IFNß and IL1ß on the production of secreted and intracellular IL1Ra in human synovial fibroblasts. Human RA synovial fibroblasts (passage 5) were left unstimulated (control; white bars) or stimulated with 2500 U/ml (10 ng/ml) ...
Figure 7
Effects of IFNß and IL1ß on the expression of sIL1Ra and icIL1Ra1 mRNA in human synovial fibroblasts. Expression levels of mRNA encoding (A) sIL1Ra and (B) icIL1Ra1 were quantified by real time RT-PCR using total RNA from human synovial ...

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