Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids.
In the cycling human endometrium, the expression of interstitial collagenase (MMP-1) and of several related matrix metalloproteinases (MMPs) follows the late-secretory fall in sex steroid plasma concentrations and is thought to be a critical step leading to menstruation. The rapid and extensive lysis of interstitial matrix that precedes menstrual shedding requires a strict control of these proteinases. However, the mechanism by which ovarian steroids regulate endometrial MMPs remains unclear. We report here that, in the absence of ovarian steroids, MMP-1 expression in endometrial fibroblasts is markedly stimulated by medium conditioned by endometrial epithelial cells. This stimulation can be prevented by antibodies directed against interleukin 1alpha (IL-1alpha) but not against several other cytokines. Ovarian steroids inhibit the release of IL-1alpha and repress MMP-1 production by IL-1alpha-stimulated fibroblasts. In short-term cultures of endometrial explants obtained throughout the menstrual cycle, the release of both IL-1alpha and MMP-1 is essentially limited to the perimenstrual phase. We conclude that epithelium-derived IL-1alpha is the key paracrine inducer of MMP-1 in endometrial fibroblasts. However, MMP-1 production in the human endometrium is ultimately blocked by ovarian steroids, which act both upstream and downstream of IL-1alpha, thereby exerting an effective control via a "double-block" mechanism.
Singer
C F
CF
Cell Biology Unit, International Institute of Cellular and Molecular Pathology, Saint-Luc University Clinics, Louvain University Medical School, 75 Avenue Hippocrate, B-1200 Brussels, Belgium.
Marbaix
E
E
Kokorine
I
I
Lemoine
P
P
Donnez
J
J
Eeckhout
Y
Y
Courtoy
P J
PJ
D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D046508:Culture Techniques; D004717:Endometrium / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1; D010053:Ovary / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013256:Steroids / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D013256:Steroids; D017364:Collagenases; D020781:Matrix Metalloproteinase 1