Synergistic effect of interleukin (IL)-1alpha and ceramide analogue on the production of IL-6, IL-8, and macrophage colony-stimulating factor by endometrial stromal cells.
OBJECTIVE
To measure the level of interleukin 6 (IL-6), IL-8, and macrophage colony-stimulating factor (M-CSF) induced by IL-1alpha in endometrial stromal cells (ESC) following treatment with ceramide analogues.


METHODS
The effects of IL-1alpha, IL-1 receptor antagonist (IL-1RA), C2-ceramide, and C6-ceramide on the production of IL-6, IL-8, and M-CSF by ESC.


METHODS
Research laboratory at Oita University Medical School.


METHODS
Eleven premenopausal women who had undergone hysterectomies for subserous myoma provided endometrial specimens in the secretory phase.


METHODS
The ESC were incubated for 24 hours with IL-1alpha, IL-1RA, C2-ceramide, and C6-ceramide.


METHODS
The levels of IL-6, IL-8, and M-CSF in the culture media were measured via enzyme-linked immunoabsorbent assay.


RESULTS
: Following stimulation by IL-1alpha, the production of IL-6, IL-8, and M-CSF showed a statistically significant increase, and they were suppressed by IL-1RA in a dose-dependent manner. Production of IL-6, IL-8, and M-CSF was not statistically significantly increased by IL-1alpha plus C2-ceramide as compared with IL-1alpha alone. Production of both IL-8 and M-CSF was statistically significantly increased by IL-1alpha plus C6-ceramide as compared with IL-1alpha alone; however, IL-6 production was not increased.


CONCLUSIONS
The results suggest that IL-1alpha stimulates the production of IL-8 and M-CSF by a mechanism that involves the sphingomyelin-ceramide system. Ceramide may be important in increasing the production of IL-8 and M-CSF in the human endometrium.
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan. kawayas@med.oita-u.ac.jp
Yasushi
Y
Kawano
Junichiro
J
Fukuda
Kaei
K
Nasu
Harunobu
H
Matsumoto
Hisashi
H
Narahara
Isao
I
Miyakawa
D000328:Adult; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D012795:Sialoglycoproteins / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017154:Stromal Cells / Q000378:metabolism
D002518:Ceramides; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; C064769:N-acetylsphingosine; D012795:Sialoglycoproteins; C101954:N-caproylsphingosine; D016173:Macrophage Colony-Stimulating Factor; D013110:Sphingosine