RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP 306
OP 314
DO 10.3899/jrheum.080318
VO 36
IS 2
A1 YASUNORI IWATA
A1 KENGO FURUICHI
A1 NORIHIKO SAKAI
A1 HIROYUKI YAMAUCHI
A1 YASUYUKI SHINOZAKI
A1 HAIYAN ZHOU
A1 YUKIE KUROKAWA
A1 TADASHI TOYAMA
A1 SHINJI KITAJIMA
A1 TOSHIYA OKUMURA
A1 SHINGO YAMADA
A1 IKURO MARUYAMA
A1 KOUJI MATSUSHIMA
A1 SHUICHI KANEKO
A1 TAKASHI WADA
YR 2009
UL http://www.jrheum.org/content/36/2/306.abstract
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.