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Prostaglandin I2 Analogs Suppress Tumor Necrosis Factor α Production and the Maturation of Human Monocyte-Derived Dendritic Cells
  1. Ching-Hui Yeh, MD*,
  2. Chang-Hung Kuo, MD†‡§,
  3. San-Nan Yang, MD, PhD‡§∥,
  4. Ming-Yii Huang, MD¶#,
  5. Hsaing-Chi Wu, MD*,
  6. Hsing-Pi Wang, MS,
  7. Thai-Hung Kuo, MD*,
  8. Chih-Hsing Hung, MD, PhD†‡§∥
  1. From the *Department of Family Medicine, Zuoying Armed Force General Hospital; †Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital; ‡Department of Pediatrics, Kaohsiung Medical University Hospital; §Graduate Institute of Medicine and ∥Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University; ¶Department of Radiation Oncology, Kaohsiung Medical University Hospital; and #Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  1. Received December 10, 2010, and in revised form June 7, 2011.
  2. Accepted for publication June 7, 2011.
  3. Reprints: Chih-Hsing Hung, MD, PhD, Department of Pediatrics, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Rd, Kaohsiung 807, Taiwan, Republic of China. E-mail: pedhung{at}gmail.com.
  4. Drs C.-H. Yeh and C.-H. Kuo contributed equally to the article.
  5. This study was supported by a grant from the Center of Excellence Environmental Medicine Kaohsiung Medical University Research Foundation (KMU-EM-97-2.2a), a grant from the Kaohsiung Medical University Hospital (KMUH-98-8G09), a grant from the Kaohsiung Municipal Ta-Tung Hospital (KMTTH-99-012), and a grant from the research program funding from the Zuoying Armed Force General Hospital (9804).

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.

Key Words
  • prostaglandin I2 analog
  • tumor necrosis factor α
  • costimulatory molecule
  • monocyte-derived dendritic cell

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