Interferon beta stimulates interleukin 1 receptor antagonist production in human articular chondrocytes and synovial fibroblasts.
BACKGROUND
Interferon (IFN) beta 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 IFNbeta on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts.


METHODS
Chondrocytes and synovial fibroblasts were stimulated with IFNbeta alone or in combination with interleukin (IL) 1beta. 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, IFNbeta alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1beta. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1beta and IFNbeta. Consistently, IL1beta and IFNbeta induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNbeta alone dose dependently increased IL1Ra secretion. In addition, IFNbeta enhanced the stimulatory effect of IL1beta on IL1Ra production. In synovial cell lysates, IFNbeta and IL1beta also increased IL1Ra levels. Consistently, IFNbeta and IL1beta induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts.


CONCLUSIONS
IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.
Palmer
G
G
Division of Rheumatology, University Hospital, and Department of Pathology, University of Geneva School of Medicine, Geneva, Switzerland.
Mezin
F
F
Juge-Aubry
C E
CE
Plater-Zyberk
C
C
Gabay
C
C
Guerne
P-A
PA
D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016899:Interferon-beta