Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9 expression and decreases proliferation, adhesion and invasion of endometrial stromal cells.
Indoleamine 2,3-dioxygenase-1 (IDO1) is an intracellular enzyme that catalyses essential amino acid tryptophan along the kynurenine pathway. The aim of this study was to determine the impact of IDO1 expression on the biological characteristic of the endometrial stromal cells (ESCs). IDO1, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) in endometriotic ectopic stromal cells, endometriosis-derived eutopic stromal cells and normal ESCs (control) were detected by the in-cell Western analysis. After being treated with lipopolysaccharide, levo-1-methyl-tryptophan (L-1-MT) alone or a combination, a comparative analysis of the above protein expression was evaluated. The effects of IDO1 on ESCs proliferation, adhesion and invasion were detected through ELISA, adhesion assay and Matrigel invasion assay, respectively. The results showed that, contrary to healthy ESCs from control women, the expression of IDO1 was significantly higher in eutopic and ectopic ESCs obtained from women with endometriosis. Inhibition of IDO1 by L-1-MT suppressed the expression of COX-2 and MMP-9 in ESCs. It could also decrease the ESCs proliferation, adhesion and invasion, while stimulating ESCs decidualization. Thus, IDO1 is possibly involved in endometriosis pathogenesis via promoting COX-2 and MMP-9 expression and regulation of ESCs biological characteristics. The information may be useful for developing a new therapeutic strategy for endometriosis.
Laboratory for Reproductive Immunology,  Hospital and Institute of Obstetrics & Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011,  China.
Jie
J
Mei
Li-Ping
LP
Jin
Ding
D
Ding
Ming-Qing
MQ
Li
Da-Jin
DJ
Li
Xiao-Yong
XY
Zhu
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism*; D003656:Decidua / Q000187:drug effects; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D007737:Kynurenine; D014364:Tryptophan; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9