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Prostaglandin I2 analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway

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Abstract

Objective and design

Although treatment for asthma control has improved a lot recently, refractory asthma is still a challenge for clinicians. Evidence revealed that anti-tumor necrosis factor (TNF)-α therapy may have potential in treating refractory asthma. Recently in an animal model, prostaglandin I2 (PGI2) analogues can suppress the cardinal feature of asthma. However, whether PGI2 analogues can regulate TNF-α expression in monocytes and the mechanism is not well-known.

Materials and methods

The human monocytes were pretreated with beraprost, iloprost and treprostinil, three PGI2 analogues, before stimulation with lipopolysaccharide (LPS). TNF-α concentration of the cell supernatants was measured by ELISA. Intracellular signaling was investigated by Western blot.

Results

PGI2 analogues suppressed LPS-induced TNF-α expression in THP-1 cells. CAY10449, an I prostanoid receptor antagonist, could reverse these effects. Beraprost increased intracellular cAMP level in THP1 cells. Forskolin, an adenylyl cyclase activator, could confer similar effect. LPS-induced TNF-α expression in THP-1 cells could be reversed by mitogen-activator protein kinase (MAPK)-p38, extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. Western blot revealed that beraprost suppressed MAPK phospho-p38, phosphor-JNK and phosphor-ERK expression.

Conclusion

PGI2 analogues suppressed LPS-induced TNF-α expression in THP-1 cells via the IP receptor-cAMP and the MAPK pathways. PGI2 analogues may have potentiality to treat asthma.

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Acknowledgments

This study was supported by a grant from Kaohsiung Medical University Hospital KMUH-98-8G09 and KMUH-99-9I08, and a grant from Kaohsiung Municipal Ta-Tung Hospital KMTTH-99-012. The project is supported by a grant from the Center of Excellence for Environmental Medicine Kaohsiung Medical University Research Foundation KMU-EM-98-4.1.

Conflict of interest

The authors declared that no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wei-Li Wang & Yu-Ting Kuo

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

    Wei-Li Wang, Chang-Hung Kuo, Yu-Te Chu, Yuh-Jyh Jong, Yu-Ting Kuo & Chih-Hsing Hung

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

    Chang-Hung Kuo & Chih-Hsing Hung

  4. Department of Pediatrics, Pingtung Christian Hospital, Pingtung, Taiwan

    Ka-Pan Lam

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

    Yuh-Jyh Jong & Chih-Hsing Hung

  6. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chang-Hung Kuo, Yuh-Jyh Jong & Chih-Hsing Hung

  7. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chih-Hsing Hung

  8. Department of Pediatrics, Yuan’s General Hospital, Kaohsiung, Taiwan

    Ching-Hua Huang

  9. Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA

    Shau-Ku Huang

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  1. Wei-Li Wang
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  2. Chang-Hung Kuo
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  3. Yu-Te Chu
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  9. Chih-Hsing Hung
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Corresponding author

Correspondence to Chih-Hsing Hung.

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Responsible Editor: Liwu Li.

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Wang, WL., Kuo, CH., Chu, YT. et al. Prostaglandin I2 analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway. Inflamm. Res. 60, 655–663 (2011). https://doi.org/10.1007/s00011-011-0317-6

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  • DOI: https://doi.org/10.1007/s00011-011-0317-6

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