Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans and interferon-gamma.
In the present study, we examined the effect of prostaglandin (PG) E2 on interleukin (IL) -12 production in monocytes stimulated with a combination of lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans and interferon-gamma (A. actinomycetemcomitans-LPS/IFN-gamma). Indomethacin, a cyclooxygenase inhibitor, enhanced IL-12 production, but inhibited PGE2 generation in A. actinomycetemcomitans-LPS/IFN-gamma-stimulated monocytes. Exogenous PGE2 inhibited IL-12 release in the cells. EP2, EP3 and EP4 receptor mRNA expression was detected in monocytes by reverse transcription-polymerase chain reaction. 11-deoxy-PGE1 (an EP2/EP4 agonist) inhibited IL-12 production in A. actinomycetemcomitans-LPS/IFN-gamma-challenged monocytes, whereas butaprost (an EP2 agonist) or ONO-AP-324 (an EP3 agonist) had no effect on IL-12 production. Dibutyryl cAMP, a cAMP analogue, and forskolin, an adenylate cyclase activator, mimicked depression of IL-12 production by PGE2. From these results, we suggest that PGE2 inhibits IL-12 production via EP4 receptors by cAMP-dependent pathways in A. actinomycetemcomitans-LPS/IFN-gamma-challenged monocytes.
Iwasaki
K
K
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. k-iwasaki.peri@tmd.ac.jp
Noguchi
K
K
Endo
H
H
Kondo
H
H
Ishikawa
I
I
D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008070:Lipopolysaccharides; C545650:PTGER4 protein, human; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D018664:Interleukin-12; D007371:Interferon-gamma; D000242:Cyclic AMP; D015232:Dinoprostone