Increased soluble interleukin-1 receptor type II proteolysis in the endometrium of women with endometriosis

Numerous functional changes were observed in the intrauterine endometrial tissue of women with endometriosis. Our previous studies revealed a marked decrease in the expression of interleukin-1 receptor type 2 (IL-1RII), a decoy receptor known for its ability to buffer IL-1 effects. The aim of the present study was to assess whether post-translational mechanisms such as proteolysis may contribute to the down-regulation of IL-1RII levels. Our data showed that soluble IL-1RII (sIL-1RII) concentrations released by freshly cultured endometrial tissue were significantly lower in women with endometriosis than in normal women (P < 0.01) and further revealed a statistically significant correlation between increased proteolysis and decreased sIL-1RII levels (P < 0.05; r = -0.47). (125)I-labelled soluble recombinant human IL-1RII ([(125)I]srhIL-1RII) was significantly more degraded in culture supernatant of tissues from women with endometriosis compared to normal women (P < 0.05), and natural tissue inhibitor of matrix metalloproteinase (TIMP)-1 inhibited [(125)I]srhIL-1RII degradation. Incubation of srhIL-1RII with active rhMMP-9 resulted in a dose-dependent degradation of srhIL-1RII as analysed by western blotting. Dual immunofluorescence showed an increased immunostaining for matrix metalloproteinase-9 in situ in the endometrial tissue of women with endometriosis compared to normal women and a decreased immunostaining for IL-1RII. The present study showed a reduced release of sIL-1RII by the endometrial tissue of women with endometriosis and revealed a proteolytic post-translational mechanism which may be involved in the down-regulation of IL-1RII levels. This may enhance IL-1-mediated activation of endometrial cells and contribute to the local immuno-inflammatory process observed in endometriosis patients.