Goffin F, Frankenne F, Béliard A, Perrier D'Hauterive S, Pignon M-R, Geenen V, Foidart J-M
Department of Tumor, University of Liège, Belgium.
Gynecol Obstet Invest. 2002;53(2):105-11. doi: 10.1159/000053003.
Metalloproteinases (MMPs) are central effectors in endometrial physiology. Their production is tightly regulated by ovarian steroids and cytokines. Using zymography, we investigated MMP-2 production by human endometrial cells treated with estradiol-17beta + progesterone (E(2)+P) and by various key cytokines in endometrial physiology (IL-1beta, LIF, TGF-beta, and TNF-alpha). No gelatinase activity was detected in the culture media of epithelial cells. In basal conditions, stromal cells produced the pro form of MMP-2. MMP-2 production/activation was not directly affected by cytokine treatment. Interestingly, activated MMP-2 was only detected after treatment of stromal cells with culture medium from epithelial cells. Cytokine treatment of epithelial cells increased the capacity of conditioned medium to stimulate stromal cells to activate MMP-2. As the tissue inhibitor of MMP-2 (TIMP-2) is a regulator of gelatinase A activity, its concentration was measured by ELISA. TIMP-2 production by stromal cells was not affected by cytokines or by epithelial cell-conditioned medium. These results strongly suggest that regulation of stromal MMP-2 activation involves soluble factor(s) derived from the epithelial compartment.
金属蛋白酶（MMPs）是子宫内膜生理过程中的关键效应分子。它们的产生受到卵巢甾体激素和细胞因子的严格调控。我们采用酶谱分析法，研究了用雌二醇 - 17β + 孕酮（E₂ + P）处理的人子宫内膜细胞以及子宫内膜生理过程中的各种关键细胞因子（IL - 1β、LIF、TGF - β和TNF - α）对MMP - 2产生的影响。上皮细胞培养基中未检测到明胶酶活性。在基础条件下，基质细胞产生MMP - 2的前体形式。细胞因子处理并未直接影响MMP - 2的产生/激活。有趣的是，仅在用上皮细胞培养基处理基质细胞后才检测到活化的MMP - 2。上皮细胞的细胞因子处理增加了条件培养基刺激基质细胞激活MMP - 2的能力。由于MMP - 2的组织抑制剂（TIMP - 2）是明胶酶A活性的调节剂，因此通过酶联免疫吸附测定法测量其浓度。基质细胞产生TIMP - 2不受细胞因子或上皮细胞条件培养基的影响。这些结果强烈表明，基质MMP - 2激活的调节涉及来自上皮区室的可溶性因子。
