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Objective. To clarify the role of T-bet in the pathogenesis of collagen-induced arthritis (CIA).Methods. T-bet-transgenic (Tg) mice under the control of the CD2 promoter were generated. CIA was induced in T-bet-Tg mice and wild-type C57BL/6 (B6) mice. Levels of type II collagen (CII)-reactive T-bet and retinoic acid receptor-related orphan nuclear receptor ␥t

I n this paper, we propose a novel test methodology f o r core-based system .LSIs. Our test methodology aims to decrease testing time for core-based system LSIs. Considering testing time reduction, our test methodology is based on B I S T and A T P G . The main contributions of this paper are summarized as follows.(9.(ii) .(iii). BIST is eficiently combined with external testing to relax the limitation of the external primary inputs and outputs. External testing f o r one of cores and B I S T s f o r the others are performed in parallel t o reduce the total testing l'ime.The testing lime minimization problem for corebased system LSIs is formulated as a combinatorial optimizai!ion problem t o select the optimal set of test vectors from given sets of test vectors f o r each core.

Human six-transmembrane epithelial antigen of prostate4 (STEAP4), an ortholog of mouse tumor necrosis factor-α-induced adipose-related protein (TIARP), plays a role in tumor necrosis factor (TNF)-dependent arthritis models. However, its role in rheumatoid arthritis (RA) is still obscure. This study explored such a role for STEAP4. The expressions of STEAP4, TNFα, and IL-6 were compared in synovia of RA and osteoarthritis patients. STEAP4 induction was examined in TNFα-stimulated fibroblast-like synoviocytes (FLS) in vitro. FLS (with/without TNFα stimulation) were also analyzed for IL-6 expression after STEAP4 knockdown, using siRNA or transfection with STEAP4-plasmid DNA. IL-8, cell proliferation, and apoptosis were also evaluated in STEAP4-overexpressing FLS. The expression of STEAP4 in joints correlated with TNFα expression, specifically in RA synovium. In the cultured FLS, STEAP4 protein expression was augmented by TNFα activation, and localized in endosomal/lysosomal compartments. STEAP4 downregulation by siRNA enhanced the expression of IL-6 mRNA, while STEAP4 overexpression suppressed IL-6 and IL-8 expression, inhibited cell proliferation, and induced apoptosis via caspase-3. The results indicated that human STEAP4 is regulated by TNFα in synovium, where it controls IL-6 secretion and proliferation of FLS, suggesting that STEAP4 might potentially suppress the pathogenesis of TNFα-induced arthritis such as RA.

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