Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.
OBJECTIVE
To determine whether leiomyoma, adenomyosis and endometrial polyps are associated with changes in uterine cavity matrix metalloproteinases (MMP-2 and MMP-9) and cytokines.


METHODS
Uterine cavity irrigation was performed in women with leiomyoma, adenomyosis and endometrial polyps, and in women with a normal uterus. MMP-2 and MMP-9 were assayed in the uterine washings by gelatin zymography. For individual subjects, the total MMP level was obtained by adding the semi-quantitative scores of band densities related to gelatinases in the zymograms. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were measured using enzyme-linked immunosorbant assay (ELISA) kits.


RESULTS
The uterine cavity of patients with leiomyoma, adenomyosis and endometrial polyps had significantly higher MMP scores than controls. Although the mean IL-1beta levels were elevated in uteri harboring a pathology compared with the normal uteri, the cytokine was significantly elevated only in the adenomyotic group. Significantly elevated levels of IFN-gamma were found in uteri with leiomyoma and endometrial polyps. Uterine washings from leiomyoma and adenomyosis contained significantly elevated mean levels of TGF-beta1 compared with controls, while TNF-alpha was significantly higher only in leiomyoma. When uterine cytokine levels were compared in relation to individual MMP levels a significant relationship was found between TGF-beta1 and elevated levels of MMP-9 and total MMPs in leiomyoma. A significant relationship was also found between IL-1beta and elevated levels of MMP-2, MMP-9 and total MMPs in the endometrial polyp group.


CONCLUSIONS
The uterine cavity in leiomyoma, adenomyosis and endometrial polyps contains elevated levels of MMPs and cytokines compared with the normal uterus. In some pathologies elevated cytokines are associated with elevated MMPs.
Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Melbourne, Vic. 3053, Australia. noborunigaki@hotmail.com
Noboru
N
Inagaki
Linh
L
Ung
Tetsuo
T
Otani
David
D
Wilkinson
Alex
A
Lopata
D016207:Cytokines / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D007889:Leiomyoma / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D011127:Polyps / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014591:Uterine Diseases / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism; D014599:Uterus / Q000737:chemistry* / Q000201:enzymology*
D016207:Cytokines; D007375:Interleukin-1; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9