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Prostaglandin I2 Analogues Enhance Growth-Related Oncogene-α Expression in Human Monocyte-Derived Dendritic Cells

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Abstract

Chemokines for neutrophils such as growth-related oncogene-α (GRO-α) are important in patients with refractory or severe asthma. Prostaglandin I2 (PGI2) analogues were regarded as potential treatments for asthma. Dendritic cells (DCs) are the professional antigen-presenting cells and play a critical role in regulating immune response. However, it is unknown whether PGI2 analogues have regulatory effects on GRO-α expression in human monocyte-derived DCs (MDDCs). The human MDDCs were pretreated with iloprost and treprostinil (two PGI2 analogues) or forskolin, a cyclic adenosine monophosphate (cAMP) activator, before stimulation with lipopolysaccharide (LPS). In some cases, I prostanoid (IP) receptor and E prostanoid (EP) antagonists were pretreated before PGI2 analogue treatment. To investigate the intracellular signaling, nuclear factor (NF)-κB inhibitor and the mitogen-activated protein kinase (MAPK) inhibitors were pretreated before PGI2 analogue treatment. GRO-α was measured by enzyme-linked immunosorbent assay. Intracellular signaling was also investigated by Western blot. Iloprost and treprostinil enhanced LPS-induced GRO-α expression in MDDCs. This effect could be reversed by an I prostanoid receptor antagonist, CAY10449, but not EP receptor antagonists. Forskolin conferred a similar modulating effect as that noted in iloprost- and treprostinil-treated MDDCs. PGI2 analogue-enhanced LPS-induced GRO-α expression was reduced by MAPK-p38 inhibitor, SB203580. PGI2 analogues enhanced LPS-induced phospho-p38 expression. PGI2 analogues enhanced LPS-induced GRO-α expression via the IP receptor–cAMP and p38-MAPK pathways in human MDDCs, which may further recruit neutrophil accumulation and adversely affect patients with refractory or severe asthma because of airway neutrophilia. These effects should be considered for PGI2 analogues as candidates for the treatment of asthma.

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Authors and Affiliations

  1. Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, Republic of China

    Chang-Hung Kuo, Yu-Te Chu, Wei-Li Wang, Tai-Heng Chen & Chih-Hsing Hung

  2. Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, Kaohsiung, 807, Taiwan, Republic of China

    Chang-Hung Kuo & Chih-Hsing Hung

  3. Department of Pediatrics, Chi Mei Medical Center, Liouying, Taiwan, Republic of China

    Ren-Long Jan

  4. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China

    Ming-Yii Huang

  5. Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

    Ming-Yii Huang

  6. Department of Pediatrics, Yuan’s General Hospital, Kaohsiung, Taiwan, Republic of China

    Ching-Hua Huang

  7. Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

    Chih-Hsing Hung

  8. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

    Chih-Hsing Hung

  9. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

    Chih-Hsing Hung

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  1. Chang-Hung Kuo
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Correspondence to Chih-Hsing Hung.

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Chang-Hung Kuo and Ren-Long Jan contributed equally to the manuscript.

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Kuo, CH., Jan, RL., Chu, YT. et al. Prostaglandin I2 Analogues Enhance Growth-Related Oncogene-α Expression in Human Monocyte-Derived Dendritic Cells. Inflammation 33, 334–343 (2010). https://doi.org/10.1007/s10753-010-9190-7

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