Prostaglandin I2 analogs suppress tumor necrosis factor α production and the maturation of human monocyte-derived dendritic cells.

ABSTRACT

BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells and have critical roles in regulating immune responses. Prostaglandin I2 (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 γ, interleukin 13 (IL-13), and IL-17A production by T cells cocultured with iloprost-treated MDDCs. RESULTS: Iloprost and treprostinil suppressed LPS-induced TNF-α 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.