Prostacyclin modulates granulocyte/macrophage colony-stimulating factor release by human blood mononuclear cells.
Although production and immunological activity of granulocyte-macrophage colony stimulating factor (GM-CSF) have been implicated in the pathogenesis of various disorders, little has been reported concerning the factors involved in the regulation of GM-CSF release. Therefore, we examined the effect of the stable prostacyclin agonist, cicaprost, on the in vitro production of GM-CSF by peripheral blood mononuclear cells (PBMC) obtained from normal subjects by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Incubation of PBMC (10(6) cells/ml1) with the bacterial lipopolysaccharide (LPS; 0.1 microgram/ml) for 24 h caused a more than 10-fold concentration-dependent increase of GM-CSF release (401 +/- 58 pg/ml x 10(6) cells-1). Addition of cicaprost (0.01 ng/ml to 1 microgram/ml) resulted in a concentration- and time-dependent reduction of LPS-induced GM-CSF secretion by PBMC with a mean IC50 of 6.7 ng/ml (n = 9). Furthermore, cicaprost also inhibited the LPS-elicited expression of GM-CSF mRNA, as determined by RT-PCR. These results demonstrate that prostacyclin inhibits LPS-induced GM-CSF release and that its effects are related to the level of transcription. Hence, our data suggest that cicaprost or related PGI2 agonists may represent immunomodulators of mononuclear cell function and may offer a therapeutic approach to GM-CSF-mediated inflammatory disorders.
Luttmann
W
W
Department of Pneumology, Medical University Clinics, Freiburg, Germany.
Herzog
V
V
Virchow
J C
JC
Matthys
H
H
Thierauch
K H
KH
Kroegel
C
C
D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D008070:Lipopolysaccharides; D011465:Prostaglandins, Synthetic; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011464:Epoprostenol; C043867:cicaprost