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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Autoimmune Diseases, CD11c Antigen, Cell Count, Cell Proliferation, Cells, Cultured, Dendritic Cells, Disease Models, Animal, Disease Progression, Enzyme Activation, Enzyme Inhibitors, HMGB1 Protein, Kidney, Lupus Nephritis, Mice, Mice, Mutant Strains, Phosphorylation, Pyrazoles, Pyridines, p38 Mitogen-Activated Protein Kinases.
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Do dendritic cells contribute to autoimmune kidney injury in MRL-Faslpr mice? Context: 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. FR167653, a specific inhibitor of p38 MAPK, was given orally from 3 months of age in MRL-Fas(lpr) mice. Cultured DC, treated with or without FR167653, were stimulated with tumor necrosis factor-alpha. 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-Fas(lpr) 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-Fas(lpr) mice followed by HMGB-1 secretion via p38 MAPK activation.
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Our results indicated that DC secrete HMGB-1 via p38 MAPK activation to participate in autoimmunity in MRL-Fas(lpr) mice. Final Decision: yes