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Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I₂ analogues

¹ Graduate Institute of Medicine, College of Medicine, ² Dept of Paediatrics, Faculty of Paediatrics, ⁴ Dept of Microbiology, Faculty of Medicine, College of Medicine, ³ Dept of Paediatrics, ⁶ Dept of Laboratory Medicine, all Kaohsiung Medical University Hospital, and ⁵ Dept of Pharmacology, Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

CORRESPONDENCE: Y-J. Jong, Dept of Paediatrics, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, Kaohsiung 807, Taiwan. Fax: 886 73213931. E-mail: yjjong{at}kmu.edu.tw

Keywords: Dendritic cell, iloprost, interferon-, interleukin-10, prostaglandin, tumour necrosis factor-

Received: May 6, 2008
Accepted September 27, 2008

Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I₂, such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI₂ analogues on cytokine expression in pDCs was investigated.

Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-, interferon (IFN)- and interleukin (IL)-10 were measured by ELISA.

Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide- (or imiquimod-) induced TNF- and IFN- production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect.

Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor- and interferon- production of human plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.

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