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Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1997 Sep 16; Vol. 94 (19), pp. 10341-5. - Publication Year :
- 1997
-
Abstract
- 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.
- Subjects :
- Cells, Cultured
Collagenases biosynthesis
Collagenases genetics
Culture Techniques
Endometrium cytology
Enzyme Activation
Female
Fibroblasts metabolism
Gene Expression Regulation, Enzymologic
Humans
Matrix Metalloproteinase 1
RNA, Messenger genetics
Collagenases metabolism
Endometrium enzymology
Interleukin-1 pharmacology
Ovary metabolism
Steroids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 94
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 9294212
- Full Text :
- https://doi.org/10.1073/pnas.94.19.10341