Endometriotic cells are resistant to interferon-gamma-induced cell growth inhibition and apoptosis: a possible mechanism involved in the pathogenesis of endometriosis.
In order to evaluate the involvement of cell proliferation and apoptosis in the pathogenesis of endometriosis, we investigated the effects of interferon-gamma (IFN-gamma) on cell growth inhibition and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSC), eutopic endometrial stromal cells with endometriosis (ESCwE) and normal endometrial stromal cells (NESC) by modified methylthiazoletetrazolium assay, 5-bromo-2'-deoxyuridine incorporation assay and internucleosomal DNA fragmentation assay. The expression of apoptosis-related molecules and IFN-gamma receptor 1 was also examined in ECSC, ESCwE and NESC using western blot analysis. IFN-gamma significantly inhibited cell proliferation and DNA synthesis of ESCwE and NESC, and induced apoptosis of these cells. In contrast, IFN-gamma did not show apparent effects on the viable cell number, DNA synthesis, or apoptosis of ECSC. An up-regulated expression of Bcl-2 and Bcl-X(L) proteins was observed in ECSC in comparison with ESCwE and NESC, whereas the levels of Bax, Bad, Fas and Fas ligand proteins in ECSC were similar to those in ESCwE and NESC. IFN-gamma receptor 1 expression was detected in ECSC, ESCwE and NESC. Enhanced expression of anti-apoptotic molecules in the ectopic endometrial cells may contribute to the development of endometriosis by conferring resistance to cytokine-induced apoptosis and increasing the chance that these cells will survive and implant outside the uterus. Further investigations on the regulation of cell proliferation in both the endometriotic and the normal endometrium may be important for the elucidation of the pathogenesis of endometriosis.
Nishida
Masakazu
M
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan.
Nasu
Kaei
K
Ueda
Tami
T
Fukuda
Junichiro
J
Takai
Noriyuki
N
Miyakawa
Isao
I
D017209:Apoptosis; D001681:Biological Assay; D049109:Cell Proliferation; D002478:Cells, Cultured; D004715:Endometriosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects; D051020:bcl-X Protein; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D017471:Receptors, Interferon; D051020:bcl-X Protein; D000096743:Interferon gamma Receptor; C494811:BCL2L1 protein, human