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.
Bellehumeur
C
C
Centre de Recherche, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Canada.
Collette
T
T
Maheux
R
R
Mailloux
J
J
Villeneuve
M
M
Akoum
A
A
D000328:Adult; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011499:Protein Processing, Post-Translational; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000378:metabolism; D012016:Reference Values; D012995:Solubility; D046509:Tissue Culture Techniques; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism / Q000494:pharmacology
D007457:Iodine Radioisotopes; D061965:Matrix Metalloproteinase Inhibitors; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9