Abstract | OBJECTIVE: METHODS: 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.
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Authors | R L Smeets, L A B Joosten, O J Arntz, M B Bennink, N Takahashi, H Carlsen, M U Martin, W B van den Berg, F A J van de Loo |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 52
Issue 7
Pg. 2202-11
(Jul 2005)
ISSN: 0004-3591 [Print] United States |
PMID | 15986350
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Il1rap protein, mouse
- Interleukin-1
- Interleukin-1 Receptor Accessory Protein
- NF-kappa B
- Proteins
- RNA, Messenger
- Receptors, Interleukin-1
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Topics |
- Adenoviridae
(genetics)
- Animals
- Arthritis, Experimental
(metabolism, pathology, therapy)
- B-Lymphocytes
(immunology, metabolism)
- Cattle
- Cell Proliferation
- Disease Models, Animal
- Gene Expression
- Genetic Therapy
- Interleukin-1
(antagonists & inhibitors, metabolism)
- Interleukin-1 Receptor Accessory Protein
- Male
- Mice
- Mice, Inbred DBA
- NF-kappa B
(genetics, metabolism)
- Proteins
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- Receptors, Interleukin-1
(antagonists & inhibitors, genetics, metabolism)
- Signal Transduction
- Spleen
(immunology, metabolism)
- T-Lymphocytes
(immunology, metabolism)
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