Activated protein C modulates the proinflammatory activity of dendritic cells.

Abstract

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 naïve 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.

• Authors: Takahiro Matsumoto, Yuki Matsushima, Masaaki Toda, Ziaurahman Roeen, Corina N D'Alessandro-Gabazza, Josephine A Hinneh, Etsuko Harada, Taro Yasuma, Yutaka Yano, Masahito Urawa, Tetsu Kobayashi, Osamu Taguchi, Esteban C Gabazza
• Journal: Journal of asthma and allergy (J Asthma Allergy) Vol. 8 Pg. 29-37 ( 2015) ISSN: 1178-6965 [Print] New Zealand
• PMID: 26005353 (Publication Type: Journal Article)