Enhanced expression of TACE contributes to elevated levels of sVCAM-1 in endometriosis.

摘要: STUDY QUESTION Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis? SUMMARY ANSWER Here we provide the first functional evidence that induced TACE human endometriotic epithelial cells is at least part responsible for enhanced release of from these cells. WHAT IS KNOWN ALREADY We others have shown serum-soluble (s)VCAM-1 are significantly higher women endometriosis, compared to disease-free controls. Experimental exists suggesting a role pathogenesis endometriosis. was identified as protease phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 murine endothelial Additionally, it has recently been upregulated endometrial luminal epithelium mid-secretory phase infertile women. DESIGN, SIZE, DURATION This study conducted Tertiary Endometriosis Referral Center Medical University Vienna. Samples total number 97 were collected between July 2013 September 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS After complete surgical exploration abdominopelvic cavity, 49 histologically proven endometriosis 48 endometriosis-free control enrolled. Each participating woman contributed only one sample eutopic endometrium normal peritoneum, some samples diverse types lesions (in 52 ectopic samples). Among 36 matched corresponding collected. In order detect protein by ELISA, peritoneal fluid (PF) 44 cases 32 controls during surgery. Expression mRNA analyzed qRT-PCR 111 tissue (28 samples, 33 50 lesions) 37 healthy peritoneum samples. Immunohistochemistry performed 123 (39 42 relation secretion examined. PMA-induced release, TACE- VCAM-1-transcripts or proteins measured an immortalized cell line (11Z) pre-incubated either inhibitors following siRNA knockdown. MAIN RESULTS AND THE ROLE OF CHANCE Here, demonstrate overexpressed both (P < 0.001 both) overexpression due activation gene transcription 0.001). Moreover, than disease High expression correlated serum 0.05) but not levels. Inhibition knockdown resulted decreased shedding vitro 0.005 P 0.01, respectively), did affect VCAM-1. observed upregulation proliferative 0.005), fertile = 0.051) without LIMITATIONS, REASONS FOR CAUTION Albeit well characterized, our population included other gynecologic diseases, which may impacted levels, e.g. benign ovarian cysts uterine fibroids. Thus, results analysis be interpreted carefully context current experimental settings. WIDER IMPLICATIONS FINDINGS The dysregulation substrate represents promising yet relatively unexplored area progression could serve basis development new treatments disease. FUNDING COMPETING INTEREST(S) work supported Ingrid Flick Foundation. authors no competing interests declare.