Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

ASC Deleted Mice Are Resistant to Collagen-Induced Arthritis

Yamazaki1,  Hideshi, Takeoka1,  Michiko, Ehara2,  Takashi, Itano1,  Naoki, Kato3,  Hiroyuki, Taniguchi1,  Shun'ichiro

Shinshu University Graduate School of Medicine, Matsumoto, Japan
Shinshu Unversity School of Medicine, Matsumoto, Japan
Shinshu University School of Medicine, Matsumoto, Japan


Although the major pro-inflammatory cytokines tumor necrosis factor a (TNFa), IL-1b, and IL-6 are all considered to be key mediators in joint inflammation and cartilage and bone destruction in rheumatoid arthritis (RA), increased attention is also being given to the involvement of IL-18 in RA pathogenesis. IL-18 and IL-1b are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), a known adapter protein that activates upstream procaspase-1. As such, we investigated the involvement of ASC in the development and progression of autoimmune arthritis.


In experiment 1, collagen-induced arthritis (CIA) was developed in highly susceptible DBA/1J mice and alterations in the expression of ASC, pro-inflammatory cytokines, and proteins were evaluated by immunohistochemistry and Western blot analysis. In experiment 2, CIA was developed in ASC-deleted (ASC-/-) mice and wild-type (ASC+/+: C57BL/6J) mice following four back-crosses to the DBA/1J background. Histological findings and expression of pro-inflammatory cytokines in knee joints were then compared between the two groups, and disease severity in joint sections was graded using a scoring system.


Experiment 1 revealed that ASC, caspase-1, IL-1b, and IL-18 were expressed in the joints of CIA mice, whereas no such expression was observed in controls. In experiment 2, histological analysis and disease scores revealed significant suppression of joint destruction in the CIA-ASC-/- mice (n=5) compared with CIA-ASC+/+ mice (n=6). Expression of IL-1b and IL-18 was also suppressed in the joints of CIA-ASC-/- mice compared with wild-type mice.


This study showed increased expression of ASC, caspase-1, IL-1b, and IL-18 in CIA mice and suppressed histological scores associated with diminished levels of IL-1b and IL-18 in the joints of CIA-ASC-/- mice. These data suggest that ASC signaling pathways that include caspase-1 activation might be involved in the exacerbation of RA. However, the expression of IL-1band IL-18 witnessed in CIA-ASC-/- mice indicates that pathways other than ASC may be involved as well.

To cite this abstract, please use the following information:
Yamazaki, Hideshi, Takeoka, Michiko, Ehara, Takashi, Itano, Naoki, Kato, Hiroyuki, Taniguchi, Shun'ichiro; ASC Deleted Mice Are Resistant to Collagen-Induced Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :9
DOI: 10.1002/art.25092

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