Up-regulation of matrix metalloproteinase-9 in human myometrium during labour: a cytokine-mediated process in uterine smooth muscle cells.
The pregnant uterus undergoes dramatic changes of tissue remodelling during the labour and post-partum period. We studied the production of matrix metalloproteinase 9 (MMP-9), as a major contributor of tissue remodelling, in human myometrium at parturition. The regulation of proMMP-9 by interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) was also investigated in human myometrial smooth muscle cells. MMP-9 was present in myometrial smooth muscle cells, interstitial fibroblasts and inflammatory cells. The gelatinolytic activities of proMMP-9 in myometrium increased dramatically during labour. IL-1beta and TNF-alpha induced proMMP-9 in myometrial smooth muscle cells, but these effects did not seem to be mediated by protein kinase C. On the other hand, neither 17beta-oestradiol nor progesterone itself affected proMMP-9 production in myometrial smooth muscle cells. Moreover, progesterone, which is known as a physiological suppressor of MMP-9 in other species, did not decrease the IL-1beta- and TNF-alpha-induced production of proMMP-9. These results suggest that IL-1beta and TNF-alpha are effective up-regulators of proMMP-9 in the tissue remodelling of human myometrium during labour.
Roh
C R
CR
Department of Obstetrics and Gynecology, Samsung Medical Center, and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea.
Oh
W J
WJ
Yoon
B K
BK
Lee
J H
JH
D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007743:Labor, Obstetric / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000166:cytology / Q000201:enzymology*; D009215:Myometrium / Q000201:enzymology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D014599:Uterus / Q000166:cytology / Q000201:enzymology*
D004792:Enzyme Precursors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9