AIMS: Inflammation plays critical roles in atherosclerosis. Chemokines are 
responsible for leukocyte trafficking and involve in inflammatory diseases. 
Macrophage inflammatory protein 1α (MIP-1α) has been implicated in 
atherosclerotic lesion formation. Prostaglandin I2 (PGI2) analog, used in 
pulmonary hypertension, has been reported to have anti-inflammatory functions. 
However, little is known about its role in the MIP-1α production in human 
monocytes.
METHODS: We investigated the effects of 3 conventional (iloprost, beraprost, and 
treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1α 
expression in human monocytes. Human primary monocytes from control subjects and 
THP-1 cell line were treated with PGI2 analogs, with or without 
lipopolysaccharide (LPS) stimulation. Supernatants were harvested to measure 
MIP-1α levels by enzyme-linked immunosorbent assay. To explore which receptors 
involved the effects of PGI2 analogs on the expression of MIP-1α expression, I 
prostanoid (IP) and E prostanoid, peroxisome proliferator-activated receptor 
(PPAR)-α, and PPAR-r receptor antagonists were used to pretreat THP-1 cells. 
Forskolin, a cyclic adenosine monophosphate (cAMP) activator, was also used to 
further confirm the cAMP involvement on the effect of PGI2 analogs in MIP-1α 
production.
RESULTS: Three PGI2 analogs could suppress LPS-induced MIP-1α production in 
THP-1 cells and human primary monocytes. ONO-1301 had a similar effect. CAY 
10449, an IP receptor antagonist, could reverse the suppressive effects on 
MIP-1α production of iloprost. Forskolin, a cAMP activator, also suppressed 
MIP-1α production in THP-1 cells.
CONCLUSIONS: Prostaglandin I2 analogs suppressed LPS-induced MIP-1α production 
in human monocytes via the IP receptor and cAMP pathway. The PGI2 analog may be 
potential in the treatment for atherosclerosis.