MATRIX METALLOPROTEINASE PRODUCTION BY CULTURED HUMAN ENDOMETRIAL STROMAL CELLS - IDENTIFICATION OF INTERSTITIAL COLLAGENASE, GELATINASE-A,GELATINASE-B, AND STROMELYSIN-1 AND THEIR DIFFERENTIAL REGULATION BY INTERLEUKIN-1-ALPHA AND TUMOR-NECROSIS-FACTOR-ALPHA
Tj. Rawdanowicz et al., MATRIX METALLOPROTEINASE PRODUCTION BY CULTURED HUMAN ENDOMETRIAL STROMAL CELLS - IDENTIFICATION OF INTERSTITIAL COLLAGENASE, GELATINASE-A,GELATINASE-B, AND STROMELYSIN-1 AND THEIR DIFFERENTIAL REGULATION BY INTERLEUKIN-1-ALPHA AND TUMOR-NECROSIS-FACTOR-ALPHA, The Journal of clinical endocrinology and metabolism, 79(2), 1994, pp. 530-536
Matrix metalloproteinases (MMPs) together degrade virtually all the co
mponents of the extracellular matrix and are likely to play a role in
remodeling of endometrial tissue during the normal menstrual cycle. Pr
imary cultures of human endometrial stromal cells secreted a number of
MMPs. MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) were
measured in culture medium by specific enzyme assays. Production of t
he enzymes did not correlate with the time of the menstrual cycle at w
hich the tissue was collected. Identities of MMP-1 and MMP-3 were conf
irmed by Western blots, by comparison of mol wt with those of purified
enzymes on casein zymography, and by inhibition of these activities w
ith EDTA and 1,10-phenanthroline. Northern analysis demonstrated speci
fic messenger ribonucleic acid for pro-MMP-1 and pro-MMP-3 in phorbol
myristate acetate-stimulated stromal cells. Two gelatinases were detec
ted by gelatin zymography: MMP-2 (gelatinase-A) was present in two for
ms (72 and 67 kilodaltons), and MMP-9 (gelatinase-B) was present as a
homodimer with a mol wt of approximately 180 kilodaltons. MMP-9, but n
ot MMP-2, secretion was stimulated by phorbol myristate acetate. All e
nzymes could be activated in vitro by (4-aminophenyl)mercuric acetate.
Both interleukin-1 alpha and tumor necrosis factor-cu stimulated the
secretion of MMP-1, MMP-3, and MMP-9, but not MMP-2, from the cells in
a concentration-dependent manner. MMP production by endometrial strom
al cells has a potentially important role in the processes of menstrua
tion and implantation.