Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells.
OBJECTIVE
To investigate whether and how P, dienogest (synthetic progestin), and danazol affected tumor necrosis factor alpha (TNFalpha)-induced interleukin-8 (IL-8) expression in endometriotic stromal cells.


METHODS
Prospective study.


METHODS
Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan.


METHODS
Ten patients who underwent laparoscopic surgery.


METHODS
Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary.


METHODS
In the presence of TNFalpha (0.1 ng/mL) and E2 (10(-7) mol/L), the cells were cultured in medium with P (10(-6) mol/L), danazol (10(-6) mol/L), or dienogest (10(-7) mol/L). The expression of the IL-8 gene and protein was determined by Northern blotting and ELISA, respectively. Activation of nuclear factor (NF)-kappaB was evaluated by electrophoretic mobility shift assay.


RESULTS
Adding TNFalpha (0.1 ng/mL) together with E2 markedly enhanced gene and protein expression of IL-8. The up-regulation of the IL-8 gene and protein expression by TNFalpha and E2 was significantly reduced by the addition of P, dienogest, or danazol. Electrophoretic mobility shift assay revealed that incubation with TNFalpha and E2 induced NF-kappaB activation. Adding P, dienogest, or danazol attenuated NF-kappaB activation.


CONCLUSIONS
The present study demonstrates for the first time that P and progestational compounds attenuate the expression of IL-8 by reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis.
Horie
Sayako
S
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan. tasuku@grape.med.tottori-u.ac.jp
Harada
Tasuku
T
Mitsunari
Masahiro
M
Taniguchi
Fuminori
F
Iwabe
Tomio
T
Terakawa
Naoki
N
D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D011446:Prospective Studies; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016209:Interleukin-8; D016328:NF-kappa B; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone