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. CONCLUSION: IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.
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. CONCLUSION:IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.
Authors: S Haskill; G Martin; L Van Le; J Morris; A Peace; C F Bigler; G J Jaffe; C Hammerberg; S A Sporn; S Fong Journal: Proc Natl Acad Sci U S A Date: 1991-05-01 Impact factor: 11.205
Authors: C H Hannum; C J Wilcox; W P Arend; F G Joslin; D J Dripps; P L Heimdal; L G Armes; A Sommer; S P Eisenberg; R C Thompson Journal: Nature Date: 1990-01-25 Impact factor: 49.962
Authors: M Muzio; N Polentarutti; M Sironi; G Poli; L De Gioia; M Introna; A Mantovani; F Colotta Journal: J Exp Med Date: 1995-08-01 Impact factor: 14.307
Authors: Hong-Hsing Liu; Yajing Hu; Ming Zheng; Megan M Suhoski; Edgar G Engleman; David L Dill; Matt Hudnall; Jianmei Wang; Rosanne Spolski; Warren J Leonard; Gary Peltz Journal: Mol Immunol Date: 2012-03-23 Impact factor: 4.407
Authors: Sarah A Woller; Cody Ocheltree; Stephanie Y Wong; Anthony Bui; Yuya Fujita; Gilson Gonçalves Dos Santos; Tony L Yaksh; Maripat Corr Journal: Brain Behav Immun Date: 2018-11-19 Impact factor: 7.217
Authors: Maripat Corr; David L Boyle; Lisa M Ronacher; Brian R Lew; Lisa G van Baarsen; Paul P Tak; Gary S Firestein Journal: Ann Rheum Dis Date: 2011-01-07 Impact factor: 19.103
Authors: J van Holten; K Pavelka; J Vencovsky; H Stahl; B Rozman; M Genovese; A J Kivitz; J Alvaro; G Nuki; D E Furst; G Herrero-Beaumont; I B McInnes; P Musikic; P P Tak Journal: Ann Rheum Dis Date: 2004-07-08 Impact factor: 19.103