Osteopontin is critically involved in rheumatoid arthritis; however, the molecular cross-talk between osteopontin and joint cell components that leads to the inflammatory joint destruction is largely unknown. We found that not only osteopontin but also tenascin-C and their common receptor, α9 integrin, are expressed at arthritic joints. The local production of osteopontin and tenascin-C is mainly due to synovial fibroblasts and, to a lesser extent, synovial macrophages. Synovial fibroblasts and macrophages express α9 integrin, and autocrine and paracrine interactions of α9 integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. α9 integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of α9 integrin function with an anti-α9 integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified α9 integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.

Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-b promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS-1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation.

Objective: To determine the clinical features of 272 patients who were diagnosed with optic neuritis at an ophthalmological clinic in Japan. Methods: We reviewed the records of patients examined between January 1977 and late June 1999. Results: The ratio of women to men was 1.7 : 1. The mean age at onset was 35 years and 80.5% were unilateral. The most frequent complaint was a vision decrease in 82.4%. The disc appeared normal in 38.5%. The median visual acuity at onset was 0.1; it was 1.0 at the recovered stage. The mean time required for visual recovery was 92.3 days from the onset. The most common known cause of optic neuritis was multiple sclerosis (MS)(22.8%). The recurrence rate was 22.0% and the mean number of recurrences was 2.9. The time for the development of disc pallor was 124.8 days. Conclusions: We found no racial difference in the incidence of MS as has been reported between Caucasians and Japanese.

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