Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis.

Gabay, C; Marinova-Mutafchieva, L; Williams, R; Gigley, J; Butler, D; Feldmann, M; Arend, W

Journal article

Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis.

Abstract:: OBJECTIVE: To examine the patterns of production of interleukin-1 receptor antagonist (IL-1Ra) isoforms and of IL-1beta during arthritis in vivo. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen, and the production of IL-1Ra isoforms was examined in whole joints and in dissected synovial tissues by reverse transcription-polymerase chain reaction (RT-PCR), RNase protection assay, Western blotting, immunostaining, and in situ hybridization. Production of IL-1beta also was examined using similar approaches. RESULTS: Production of IL-1Ra increased in the joints during collagen-induced arthritis (CIA). By RT-PCR, secreted IL-1Ra messenger RNA (mRNA) was detected in normal joints, whereas intracellular IL-1Ra type I (icIL-1Ra1) mRNA was only produced in inflamed joints. Western blot studies showed that icIL-1Ra1 protein levels increased in the joints during the course of CIA and that icIL-1Ra3 protein was also present in low amounts. RNase protection assays showed that the IL-1beta:IL-1Ra mRNA ratio was increased in inflamed joints through day 14 of arthritis, whereas a reverse pattern was present at later time points (from day 20 to day 60). Consistent with this finding, immunohistochemistry and in situ hybridization studies confirmed that icIL-1Ra1 was only present in inflamed joints. The histologic evaluation of CIA during the course of the disease indicated a resolution of acute inflammation, since icIL-1Ra1 production increased and the ratio of IL-1beta to total IL-1Ra decreased. CONCLUSION: Production of IL-1Ra isoforms, particularly icIL-1Ra1, is stimulated in inflamed joints during CIA in mice. The combination of decreased production of IL-1beta and elevated levels of icIL-1Ra1 during the course of CIA was associated with a reduction in inflammatory activity. These results suggest that icIL-1Ra1 may play a role in the resolution of murine CIA.

Publication status:: Published

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APA Style

Gabay, C., Marinova-Mutafchieva, L., Williams, R., Gigley, J., Butler, D., Feldmann, M., & Arend, W. (2001). Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis. Arthritis and Rheumatism, 44(2), 451–462.

MLA Style

Gabay, C, et al. “Increased Production of Intracellular Interleukin-1 Receptor Antagonist Type I in the Synovium of Mice with Collagen-Induced Arthritis: a Possible Role in the Resolution of Arthritis.” Arthritis and Rheumatism, vol. 44, no. 2, 2001, pp. 451–62.

Chicago Style

Gabay, C, L Marinova-Mutafchieva, R Williams, et al. 2001. “Increased Production of Intracellular Interleukin-1 Receptor Antagonist Type I in the Synovium of Mice with Collagen-Induced Arthritis: a Possible Role in the Resolution of Arthritis.” Arthritis and Rheumatism 44 (2): 451–62.
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