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http://purl.uniprot.org/citations/15986350http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15986350http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15986350http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To discern the mode of interleukin-1 (IL-1) inhibition of soluble IL-1 receptor accessory protein (sIL-1RAcP) by comparison with IL-1 receptor antagonist (IL-1Ra) in arthritis.

Methods

Adenoviral vectors encoding either sIL-1RAcP or IL-1Ra were administered systemically before onset of collagen-induced arthritis in DBA/1 mice. Anti-bovine type II collagen IgG and IL-6 were quantified in serum. Proliferative response of splenic T cells was determined in the presence of sIL-1RAcP or IL-1Ra. The effect on IL-1 inhibition of recombinant sIL-1RAcP and IL-1Ra was further examined in vitro, using NF-kappaB luciferase reporter cell lines. Quantitative polymerase chain reaction was used to determine the relative messenger RNA expression of the IL-1 receptors.

Results

Adenoviral overexpression of both sIL-1RAcP and IL-1Ra resulted in amelioration of the collagen-induced arthritis. Both IL-1 antagonists reduced the circulating levels of antigen-specific IgG2a antibodies, but only IL-1Ra was able to inhibit lymphocyte proliferation. By using purified lymphocyte populations derived from NF-kappaB reporter mice, we showed that sIL-1RAcP inhibits IL-1-induced NF-kappaB activity in B cells but not T cells, whereas IL-1Ra inhibited IL-1 on both cell types. A study in a panel of NF-kappaB luciferase reporter cells showed that the sIL-1RAcP inhibits IL-1 signaling on cells expressing either low levels of membrane IL-1RAcP or high levels of IL-1RII.

Conclusion

We show that the sIL-1RAcP ameliorated experimental arthritis without affecting T cell immunity, in contrast to IL-1Ra. Our results provide data in support of receptor competition by sIL-1RAcP as an explanation for the different mode of IL-1 antagonism in comparison with IL-1Ra."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.org/dc/terms/identifier"doi:10.1002/art.21108"xsd:string
http://purl.uniprot.org/citations/15986350http://purl.org/dc/terms/identifier"doi:10.1002/art.21108"xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Takahashi N."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Takahashi N."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Joosten L.A."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Joosten L.A."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Bennink M.B."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Bennink M.B."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"van de Loo F.A."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"van de Loo F.A."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"van den Berg W.B."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"van den Berg W.B."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Arntz O.J."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Arntz O.J."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Carlsen H."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Carlsen H."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Martin M.U."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Martin M.U."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Smeets R.L."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/author"Smeets R.L."xsd:string
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15986350http://purl.uniprot.org/core/date"2005"xsd:gYear
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