Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
ASC Plays a Role in the Priming Phase of the Immune Response to Type II Collagen in Collagen-Induced Arthritis.
Yamazaki1, Hideshi, Takeoka1, Michiko, Kitazawa1, Masato, Ehara2, Takashi, Itano1, Naoki, Kato2, Hiroyuki, Taniguchi1, Shun'ichiro
Although rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, the role of TNF-a, IL-1b, IL-18, and IL-6 in the pathogenesis of RA has been well established. IL-1b and IL-18 are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), which is an adaptor protein that activates procaspase-1. We therefore investigated the involvement of ASC in RA progression and assessed the phase at which ASC exerts effects using ASC-deficient mice models of collagen-induced-arthritis (CIA) and collagen antibody-induced arthritis (CAIA).
CIA was developed in ASC-deficient (ASC-/-) and wild-type (ASC+/+) mice by four back-crosses to the DBA/1J background. CAIA was induced in ASC-/- and ASC+/+ mice using a mouse monoclonal anti-type II collagen five clone antibody cocktail. Histological findings and expression of pro-inflammatory cytokines in knee joints were then compared and disease severity in joint sections was graded using a scoring system. Analysis of IL-1b and IL-18 expression was also performed by immunohistochemistry.
Histological examination and scoring of arthritic knee joints from ASC+/+ and ASC-/- CIA mice revealed that infiltration of inflammatory cells and cartilage/bone destruction were significantly decreased in ASC-/- mice compared with ASC+/+ mice. Conversely, no differences were observed between ASC-deficient mice and controls for CAIA. In CIA knee joints, IL-1b and IL-18 expression were lower in ASC-/- mice compared with ASC+/+ mice, whereas these cytokines were expressed at similar levels in the knee joints of ASC+/+ and ASC-/- CAIA mice.
We demonstrated that ASC-deficient mice were comparably susceptible to CAIA as normal mice, but were protected from disease severity in CIA. Thus, ASC is believed to be involved in early CIA development and may play a role in the priming phase of the immune response to type II collagen.
To cite this abstract, please use the following information:
Yamazaki, Hideshi, Takeoka, Michiko, Kitazawa, Masato, Ehara, Takashi, Itano, Naoki, Kato, Hiroyuki, et al; ASC Plays a Role in the Priming Phase of the Immune Response to Type II Collagen in Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1709