Erschienen in:
01.07.2011 | Original Research Paper
Prostaglandin I2 analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway
verfasst von:
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
Erschienen in:
Inflammation Research
|
Ausgabe 7/2011
Einloggen, um Zugang zu erhalten
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.