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Effect of prostaglandin I2 analogs on monocyte chemoattractant protein-1 in human monocyte and macrophage

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Abstract

Chemokines play essential roles during inflammatory responses and in pathogenesis of inflammatory diseases. Monocyte chemotactic protein-1 (MCP-1) is a critical chemokine in the development of atherosclerosis and acute cardiovascular syndromes. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space that leads to atherosclerotic plaque formation. Prostaglandin I2 (PGI2) analogs are used clinically for patients with pulmonary hypertension and have anti-inflammatory effects. However, little is known about the effect of PGI2 analogs on the MCP-1 production in human monocytes and macrophages. We investigated the effects of three conventional (iloprost, beraprost and treprostinil) and one new (ONO-1301) PGI2 analogs, on the expression of MCP-1 expression in human monocytes and macrophages. Human monocyte cell line, THP-1 cell, was treated with PGI2 analogs after LPS stimulation. Supernatants were harvested to measure MCP-1 levels and measured by ELISA. To explore which receptors involved the effects of PGI2 analogs on the expression of MCP-1 expression, IP and EP, PPAR-α and PPAR-γ receptor antagonists were used. Forskolin, a cAMP activator, was used to further confirm the involvement of cAMP on MCP-1 production in human monocytes. Three PGI2 analogs suppressed LPS-induced MCP-1 production in THP-1 cells and THP-1-induced macrophages. Higher concentrations of ONO-1301 also had the suppressive effect. CAY 10449, an IP receptor antagonist, could reverse the effects on MCP-1 production of iloprost on THP-1 cells. Other reported PGI2 receptor antagonists including EP1, EP2, EP4, PPAR-α and PPAR-γ antagonists could not reverse the effect. Forskolin, a cAMP activator, also suppressed MCP-1 production in THP-1 cells. PGI2 analogs suppressed LPS-induced MCP-1 production in human monocytes and macrophages via the IP receptor and cAMP pathway. The new PGI2 analog (ONO-1301) was not better than conventional PGI2 analog in the suppression of MCP-1 production in human monocytes.

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Acknowledgments

This study was supported by grants from Medical Research Fund (No. 101-06 and 101-03) of Kaohsiung Armed Forces General Hospital and from National Science Council (NSC 102-2314-B-037-052 and NSC 102-2314-B-037-048) of the Republic of China, and Kaohsiung Medical University Hospital Research Foundation KMUH102-2T04, grants from Kaohsiung Municipal Ta-Tung Hospital KMTTH-101-009, KMTTH-102-002, KMTTH 102-008 and grants from Kaohsiung Municipal Hsiao-Kang Hospital, Kmhk-102-007.

Conflict of Interest

All authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, ROC

    Ming-Kai Tsai

  2. Department of Nursing, MeiHo University, Pingtung, Taiwan, ROC

    Ming-Kai Tsai

  3. Division of Cardiac Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Chong-Chao Hsieh

  4. Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Hsuan-Fu Kuo

  5. Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ROC

    Min-Sheng Lee & Chang-Hung Kuo

  6. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, #100, Tz-You 1st Road, Kaohsiung, 807, Taiwan, ROC

    Min-Sheng Lee, Chang-Hung Kuo & Chih-Hsing Hung

  7. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC

    Ming-Yii Huang

  8. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Chang-Hung Kuo & Chih-Hsing Hung

  9. Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan, ROC

    Chih-Hsing Hung

  10. Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Chih-Hsing Hung

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  1. Ming-Kai Tsai
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  2. Chong-Chao Hsieh
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  3. Hsuan-Fu Kuo
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  4. Min-Sheng Lee
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  5. Ming-Yii Huang
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  6. Chang-Hung Kuo
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  7. Chih-Hsing Hung
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Corresponding author

Correspondence to Chih-Hsing Hung.

Additional information

Ming-Kai Tsai, Chong-Chao Hsieh, Chang-Hung Kuo and Chih-Hsing Hung have contributed equally to this work.

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Tsai, MK., Hsieh, CC., Kuo, HF. et al. Effect of prostaglandin I2 analogs on monocyte chemoattractant protein-1 in human monocyte and macrophage. Clin Exp Med 15, 245–253 (2015). https://doi.org/10.1007/s10238-014-0304-7

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  • DOI: https://doi.org/10.1007/s10238-014-0304-7

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