Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts.
OBJECTIVE
The aim of this study was to compare the anti-inflammatory effect of proteoglycan (PG) with that of progesterone (P) in the cultured fibroblasts from human uterine cervix.


METHODS
After obtaining informed consent, the cervix was collected from normal women undergoing total hysterectomy. The cervix was cultured until fibroblasts proliferated and had grown to confluence, then, the fibroblasts were stimulated by lipopolysaccharide (LPS) with or without PG, P and a combination of both; they were cultured for 24-48 h. The anti-inflammatory effects of PG and P were evaluated by the suppression of IL-6 or IL-8 secretion. The expression of the IL-6 or IL-8 gene and the expression of their protein were determined by real-time PCR, and ELISA, respectively. Activation of Toll-like receptor (TLR) 4 was evaluated by Western blotting.


RESULTS
LPS markedly enhanced gene and protein expression of IL-6 and IL-8 in human uterine cervical fibroblasts. The up-regulation of the IL-6 or IL-8 gene and protein expression by LPS was significantly suppressed with PG, P and a combination of both. Western blotting revealed that combination of PG and P showed more potent inhibition on LPS-stimulated TLR4 induction than that seen by each.


CONCLUSIONS
This study showed that both PG and P have an inhibitory effect on LPS-induced inflammation. This anti-inflammatory effect of PG and P was augmented by co-administration of both, suggesting for the first time that PG has an anti-inflammatory effect on human uterine cervical fibroblasts.
Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. a-fuku@cc.hirosaki-u.ac.jp
Asami
A
Fukuyama
Kanji
K
Tanaka
Ikuko
I
Kakizaki
Kosuke
K
Kasai
Mitsuru
M
Chiba
Toshiya
T
Nakamura
Hideki
H
Mizunuma
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000276:immunology / Q000494:pharmacology*; D011509:Proteoglycans / Q000276:immunology / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011509:Proteoglycans; D051197:Toll-Like Receptor 4; D011374:Progesterone