PT - JOURNAL ARTICLE 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 TI - Dendritic Cells Contribute to Autoimmune Kidney Injury in MRL-Fas<sup>lpr </sup> Mice AID - 10.3899/jrheum.080318 DP - 2009 Jan 15 TA - The Journal of Rheumatology PG - jrheum.080318 4099 - http://www.jrheum.org/content/early/2009/01/22/jrheum.080318.short 4100 - http://www.jrheum.org/content/early/2009/01/22/jrheum.080318.full AB - 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.