Prostaglandin i₂ analogs suppress tumor necrosis factor α production and the maturation of human monocyte-derived dendritic cells

Background: Dendritic cells (DCs) are professional antigen-presenting cells and have critical roles in regulating immune responses. Prostaglandin I ₂ (PGI₂) analogs are considered to be potential treatments for asthma. However, the effect of PGI₂ analogs on human monocyte-derived DCs (MDDCs) is still not clearly understood. Methods: Human MDDCs were pretreated with iloprost and treprostinil (2 PGI₂ analogs) or forskolin (an adenyl cyclase activator) before lipopolysaccharide (LPS) stimulation. In some cases, I prostanoid (IP) receptor and E prostanoid receptor antagonists were added before the PGI₂ analog treatment. tumor necrosis factor α (TNF-α) was measured by enzyme-linked immunosorbent assay. The expression of costimulatory molecules was assessed by flow cytometry. T-cell polarization function was investigated by measuring interferon F, interleukin 13 (IL-13), and IL-17A production by T cells cocultured with iloprosttreated MDDCs. Results: Iloprost and treprostinil suppressed LPS-induced TNF-> expression in MDDCs. This effect could be reversed by an IP receptor antagonist, CAY10449, but not by E prostanoid receptor antagonists. Forskolin conferred a similar effect. Iloprost suppressed the LPS-induced expression of costimulatory molecules, including CD80, CD86, CD40 and HLA-DR. Iloprost-treated MDDCs increased IL-17A production by T cells. Conclusions: Prostaglandin I₂ analogs may exert anti-inflammatory effects by suppressing TNF-α expression via the IP receptor-cyclic adenosine monophosphate pathways and by inhibiting the expression of costimulatory molecules in human MDDCs.