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 I(2) 
(PGI(2)) analogues can suppress the cardinal feature of asthma. However, whether 
PGI(2) 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 PGI(2) 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: PGI(2) 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: PGI(2) analogues suppressed LPS-induced TNF-α expression in THP-1 
cells via the IP receptor-cAMP and the MAPK pathways. PGI(2) analogues may have 
potentiality to treat asthma.