Chemokines for neutrophils such as growth-related oncogene-alpha (GRO-alpha) are 
important in patients with refractory or severe asthma. Prostaglandin I(2) 
(PGI(2)) analogues were regarded as potential treatments for asthma. Dendritic 
cells (DCs) are the professional antigen-presenting cells and play a critical 
role in regulating immune response. However, it is unknown whether PGI(2) 
analogues have regulatory effects on GRO-alpha expression in human 
monocyte-derived DCs (MDDCs). The human MDDCs were pretreated with iloprost and 
treprostinil (two PGI(2) analogues) or forskolin, a cyclic adenosine 
monophosphate (cAMP) activator, before stimulation with lipopolysaccharide 
(LPS). In some cases, I prostanoid (IP) receptor and E prostanoid (EP) 
antagonists were pretreated before PGI(2) analogue treatment. To investigate the 
intracellular signaling, nuclear factor (NF)-kappaB inhibitor and the 
mitogen-activated protein kinase (MAPK) inhibitors were pretreated before PGI(2) 
analogue treatment. GRO-alpha was measured by enzyme-linked immunosorbent assay. 
Intracellular signaling was also investigated by Western blot. Iloprost and 
treprostinil enhanced LPS-induced GRO-alpha expression in MDDCs. This effect 
could be reversed by an I prostanoid receptor antagonist, CAY10449, but not EP 
receptor antagonists. Forskolin conferred a similar modulating effect as that 
noted in iloprost- and treprostinil-treated MDDCs. PGI(2) analogue-enhanced 
LPS-induced GRO-alpha expression was reduced by MAPK-p38 inhibitor, SB203580. 
PGI(2) analogues enhanced LPS-induced phospho-p38 expression. PGI(2) analogues 
enhanced LPS-induced GRO-alpha expression via the IP receptor-cAMP and p38-MAPK 
pathways in human MDDCs, which may further recruit neutrophil accumulation and 
adversely affect patients with refractory or severe asthma because of airway 
neutrophilia. These effects should be considered for PGI(2) analogues as 
candidates for the treatment of asthma.