title: Anti-inflammatory effects of activated protein C on human dendritic cells.
abstract: Activated protein C (APC) has an anticoagulant action and plays an important role in blood coagulation homeostasis. In addition to its anticoagulant action, APC is known to have cytoprotective effects, such as anti-apoptotic action and endothelial barrier protection, on vascular endothelial cells and monocytes. However, the effects of APC on DCs have not been clarified. To investigate the effects of APC on human DCs, monocytes were isolated from peripheral blood and DC differentiation induced with LPS. APC significantly inhibited the production of inflammatory cytokines TNF-α and IL-6 during differentiation of immature DCs to mature DCs, but did not inhibit the production of IL-12 and anti-inflammatory cytokine IL-10. Interestingly, treatment with 5 μg/mL, but not 25 μg/mL, of APC significantly enhanced production of IL-10. In addition, protein C, which is the zymogen of APC, did not affect production of these cytokines. On the other hand, flow cytometric analysis of DC's surface molecules indicated that APC does not significantly affect expression of CD83, a marker of mDC differentiation, and the co-stimulatory molecules CD40, CD80 and CD86. These results suggest that APC has anti-inflammatory effects on human DCs and may be effective against some inflammatory diseases in which the pathogenesis involves TNF-α and/or IL-6 production.
authors.affiliation: Development Department, Blood Plasma Division, Chemo-Sero-Therapeutic Research Institute (Kaketsuken).|Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohkuma
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Goto
authors.affiliation: Development Department, Blood Plasma Division, Chemo-Sero-Therapeutic Research Institute (Kaketsuken).
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kamei
authors.affiliation: Development Department, Blood Plasma Division, Chemo-Sero-Therapeutic Research Institute (Kaketsuken).
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Hamamoto
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D011486:Protein C / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D015850:Interleukin-6; D011486:Protein C; D016753:Interleukin-10; D018664:Interleukin-12
keywords: activated protein C; dendritic cells; interleukin-6; tumor necrosis factor-α