Synergistic effect of interleukin-1alpha and ceramide analogue on production of prostaglandin E2 and F2alpha by endometrial stromal cells.
OBJECTIVE
Prostaglandins (PGs) are synthesized in the endometrium. Our objective was to evaluate interleukin (IL)-1alpha-induced production of PGE2 and PGF2alpha in endometrial stromal cells (ESC) following treatment with ceramide analogues.


METHODS
ESC were obtained from human uterine endometrium by enzymic digestion and filtration. ESC were treated with IL-1alpha, IL-1 receptor antagonist (ra), C2-ceramide and C6-ceramide. The concentrations of PGE2 and PGF2alpha in media were determined using ELISA. The induction of prostaglandin H synthase (PGHS)-2 mRNA was also ascertained by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
The production of PGE2 and PGF2alpha was significantly increased by IL-lalpha and suppressed by IL-1 ra, in a dose-dependent manner. PGF2alpha production was further increased by treatment with the combination of IL-1alpha and C2-ceramide as compared with IL-1alpha treatment alone. There was no significant difference in PGE2 production between cells treated with IL-1alpha and C2-ceramide and those treated with IL-1alpha alone. Both PGE2 and PGF2alpha production were significantly increased by treatment with IL-1alpha and C6-ceramide as compared with IL-1alpha treatment alone. Treatment of ESC with IL-1alpha stimulated PGHS-2 mRNA. PGHS-2 mRNA was decreased when IL-1 ra was added to the IL-1alpha-stimulated cells.


CONCLUSIONS
These results suggest that IL-1alpha stimulates the production of PGE2 and PGF2alpha by a mechanism that involves the sphingomyelin-ceramide system, and thus that ceramide may be important in increasing the production of PGE2 and PGF2alpha in the human endometrium.
Kawano
Y
Y
Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Japan.
Nakamura
S
S
Fukuda
J
J
Miyakawa
I
I
D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002518:Ceramides; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C064769:N-acetylsphingosine; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C101954:N-caproylsphingosine; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013110:Sphingosine