@phdthesis{oai:mie-u.repo.nii.ac.jp:00013521, author = {Matsumoto, Takahiro and 松本, 貴博}, month = {Dec}, note = {application/pdf, Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naive CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice. Conclusion: These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation., 本文/Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 9p}, school = {三重大学}, title = {Activated protein C modulates the proinflammatory activity of dendritic cells}, year = {2015}, yomi = {マツモト, タカヒロ} }