Prostaglandin F(2alpha), cytokines and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells.
Human uterine cervical tissue is composed mainly of fibroblast cells and the extracellular matrix in which collagen types I and III predominate. It is hypothesized that these collagens are degraded by matrix metalloproteinases (MMPs) in the initial step of uterine cervical ripening during parturition. Among the MMPs, MMP-1, -8 and -13 have substrate selectivity for collagen types I and III. In the present study, we examined the regulation of MMP-1 secretion from the human uterine cervix. Immunohistochemistry detected strong staining of MMP-1, but not of MMP-8 or -13, in stromal cells of the pregnant uterine cervix. The MMP-1 expression in the pregnant uterine cervix was further confirmed by Western blot analysis and RT-PCR. To clarify the regulation of MMP-1 production, we subsequently investigated the effects of prostaglandins, inflammatory cytokines and cyclic mechanical stretch on the secretion of MMP-1 from cultured human uterine cervical fibroblast cells. Treatment with prostaglandin (PG)F(2alpha) (10(-7) to 10(-5) mol/l) or interleukin (IL)-1alpha (0.01-1.0 ng/ml) or stimulation with cyclic mechanical stretch increased MMP-1 secretion from cultured human uterine cervical fibroblast cells, with maximal increases of 3.4-, 4.5- and 1.9-fold respectively (24 h of treatment, P < 0.05 for all comparisons). These data suggest that MMP-1 may play a significant role in the degradation of extracellular collagen types I and III in the pregnant uterine cervix during the process of cervical ripening, in response to various stimulations such as PGF(2alpha), IL-1alpha and mechanical stretch.
Yoshida
Masahiro
M
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Sagawa
Norimasa
N
Itoh
Hiroaki
H
Yura
Shigeo
S
Takemura
Maki
M
Wada
Yukihisa
Y
Sato
Takashi
T
Ito
Akira
A
Fujii
Shingo
S
D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism*; D003474:Curcumin / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D011247:Pregnancy; D013314:Stress, Mechanical
D007375:Interleukin-1; D015237:Dinoprost; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1; D003474:Curcumin; D015232:Dinoprostone