TY - JOUR T1 - Dendritic Cells Contribute to Autoimmune Kidney Injury in MRL-<em>Fas</em><em><sup>lpr</sup></em> Mice JF - The Journal of Rheumatology JO - J Rheumatol SP - 306 LP - 314 DO - 10.3899/jrheum.080318 VL - 36 IS - 2 AU - YASUNORI IWATA AU - KENGO FURUICHI AU - NORIHIKO SAKAI AU - HIROYUKI YAMAUCHI AU - YASUYUKI SHINOZAKI AU - HAIYAN ZHOU AU - YUKIE KUROKAWA AU - TADASHI TOYAMA AU - SHINJI KITAJIMA AU - TOSHIYA OKUMURA AU - SHINGO YAMADA AU - IKURO MARUYAMA AU - KOUJI MATSUSHIMA AU - SHUICHI KANEKO AU - TAKASHI WADA Y1 - 2009/02/01 UR - http://www.jrheum.org/content/36/2/306.abstract N2 - Objective. Dendritic cells (DC) contribute to autoimmune disease progression and pathogenesis. Mature DC have been reported to secrete high mobility group box protein (HMGB-1), a novel inflammatory cytokine, via p38 mitogen-activated protein kinase (MAPK) activation. We investigated whether DC are involved in progression of autoimmune diseases followed by secretion of HMGB-1 via p38 MAPK activation in a lupus-prone mouse model. Methods. FR167653, a specific inhibitor of p38 MAPK, was given orally from 3 months of age in MRL-Faslpr mice. Cultured DC, treated with or without FR167653, were stimulated with tumor necrosis factor-α. Results. Inhibition of p38 MAPK led to a reduction in the number of CD11c-positive cells, including those with the mature phenotype, in the diseased kidney and spleen, which resulted in improvement of kidney pathology in MRL-Faslpr mice. The number of CD11c-positive cells in circulation was also reduced. HMGB-1 protein and transcripts detected in the diseased kidney, and the number of cells dual-positive for HMGB-1 and CD11c, were reduced by inhibition of p38 MAPK. Maturation of cultured DC and increased cytokines, including HMGB-1, in the supernatant were inhibited by FR167653 treatment. These results suggest that DC are involved in the progression of autoimmune kidney diseases in MRL-Faslpr mice followed by HMGB-1 secretion via p38 MAPK activation. Conclusion. Our results indicated that DC secrete HMGB-1 via p38 MAPK activation to participate in autoimmunity in MRL-Faslpr mice. ER -