Inflammation Research

, Volume 60, Issue 7, pp 655–663 | Cite as

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

  • Wei-Li Wang
  • Chang-Hung Kuo
  • Yu-Te Chu
  • Ching-Hua Huang
  • Ka-Pan Lam
  • Shau-Ku Huang
  • Yuh-Jyh Jong
  • Yu-Ting Kuo
  • Chih-Hsing Hung
Original Research Paper


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.


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.


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.


Tumor necrosis factor α I prostanoid receptor MAPK pathway Monocytes Prostaglandin I2 



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.


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Wei-Li Wang
    • 1
    • 2
  • Chang-Hung Kuo
    • 2
    • 3
    • 6
  • Yu-Te Chu
    • 2
  • Ching-Hua Huang
    • 8
  • Ka-Pan Lam
    • 4
  • Shau-Ku Huang
    • 9
  • Yuh-Jyh Jong
    • 2
    • 5
    • 6
  • Yu-Ting Kuo
    • 1
    • 2
  • Chih-Hsing Hung
    • 2
    • 3
    • 5
    • 6
    • 7
  1. 1.Department of Emergency MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Department of PediatricsKaohsiung Medical University HospitalKaohsiungTaiwan, ROC
  3. 3.Department of PediatricsKaohsiung Municipal Ta-Tung HospitalKaohsiungTaiwan
  4. 4.Department of PediatricsPingtung Christian HospitalPingtungTaiwan
  5. 5.Department of Pediatrics, Faculty of MedicineCollege of Medicine, Kaohsiung Medical UniversityKaohsiungTaiwan
  6. 6.Graduate Institute of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  7. 7.Center of Excellence for Environmental MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  8. 8.Department of PediatricsYuan’s General HospitalKaohsiungTaiwan
  9. 9.Johns Hopkins Asthma and Allergy CenterJohns Hopkins University School of MedicineBaltimoreUSA

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