Interleukin-1 receptor-ligand interactions modulate interstitial collagenase-1 production by human endometrial fibroblasts

The expression of interstitial collagenase-1 in the cycling human endometrium is restricted to the perimenstrual phase and is a key event for matrix degradation that initiates menstruation. In the absence of ovarian steroids, collagenase production by endometrial fibroblasts is induced by epithelial cell-derived interleukin-1alpha. Media conditioned by endometrial epithelial cells were found to contain interleukin-1alpha but not interleukin-1beta, and their capacity to induce collagenase production by endometrial fibroblasts correlated with interleukin-1alpha concentration in a saturable manner. Collagenase induction by recombinant interleukin-1alpha was severely inhibited by interleukin-1 receptor antagonist alone and abolished by its combination with soluble interleukin-1 type-II receptor. By contrast, the association of the receptor antagonist with soluble type-I receptor was less effective than each factor alone. Induction of collagenase by epithelial cell-conditioned media was severely inhibited by neutralizing interleukin-1alpha antibodies, whereas the combination of receptor antagonist with soluble type-II receptor proved less effective. We conclude that the collagenase response of endometrial fibroblasts to epithelial cell-derived interleukin-1alpha is effectively blocked in vitro by soluble members of the interleukin-1 family and can thus be modulated in vivo by these or other local factors.