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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 antitumor 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-cAMPand the MAPK pathways. PGI2 analogues may have potentiality to treat asthma.

Original languageEnglish
Pages (from-to)655-663
Number of pages9
JournalInflammation Research
Volume60
Issue number7
DOIs
Publication statusPublished - Jul 1 2011
Externally publishedYes

Keywords

  • I prostanoid receptor
  • MAPK pathway
  • Monocytes
  • Prostaglandin I
  • Tumor necrosis factor a

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

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    Wang, W. L., Kuo, C. H., Chu, Y. T., Huang, C. H., Lam, K. P., Huang, S. K., Jong, Y. J., Kuo, Y. T., & Hung, C. H. (2011). Prostaglandin I2 analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway. Inflammation Research, 60(7), 655-663. https://doi.org/10.1007/s00011-011-0317-6