Prostaglandin E-2 stimulates AP-1-mediated CD14 expression in mouse macrophages via cyclic AMP-dependent protein kinase A

PGs play a functional role in the early stage of Gram-negative bacterial in fections, because this prostanoid is produced rapidly by epithelial cells a fter a bacterial infection. CD14, one of the LPS receptors, is a key molecu le in triggering the response to bacterial LPS in association with a Toll-l ike molecule. Therefore, in this study, we investigated the effect of PG on CD14 expression in mouse macrophages. PGE(1), PGE(2), and PGA(1) among the PGs tested strongly stimulated the expression of the CD14 gene in the cell s, The stimulatory action also was observed by Western blot analysis. cAMP elevating agents stimulated expression of CD14 gene as well, Protein kinase A inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide ( H-89), but not protein kinase C inhibitor 3-{1-[3-(dimethylamino)propyl]-1H -indol-3-yl}-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione (GF109203X), abolished the stimulated expression of CD14, A run-on assay showed that PGE(2) stimul ated the CD14 gene expression at the transcriptional level via protein kina se A. PGE(2) also stimulated activation of AP-1, a heterodimer of c-Jun and c-Fos, because the prostanoid increased specific binding of nuclear protei ns to the AP-1 consensus sequence and stimulated AP-1-promoted luciferase a ctivity, PGE(2)-stimulated expression of CD14 was inhibited by antisense c- fos and c-jun oligonucleotides, but not by their sense oligonucleotides, Fi nally, PGE(2) pretreatment synergistically stimulated LPS-induced expressio n of IL-1 beta and IL-6 genes in mouse macrophages, Therefore, the present study demonstrates that PGE(2) has the ability to stimulate AP-1-mediated e xpression of CD14 in mouse macrophages via cAMP-dependent protein kinase A.