RESUMEN
The use of anti-L1-cell adhesion molecule monoclonal antibodies (anti-L1CAM-mAb) in an endometriosis epithelial cell line Z12 led to a statistically significant decrease in cell proliferation and cell invasion and to an inhibition of the adhesion compared with unspecific IgG-Ab treated and untreated cells. Because it increases the cell invasion and adhesion which consequently aggravates the disease, L1 could possibly promote endometriosis development; thus, further studies should evaluate the possible use of anti-L1-mAb in an animal endometriosis model.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Endometriosis/patología , Molécula L1 de Adhesión de Célula Nerviosa/inmunología , Enfermedades Peritoneales/patología , Adhesión Celular/efectos de los fármacos , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Modelos Biológicos , Molécula L1 de Adhesión de Célula Nerviosa/antagonistas & inhibidoresRESUMEN
Apoptosis is a physiologic process that eradicates undesired cells without inducing an inflammatory reaction. It is an important regulator of eutopic endometrial function and evidence suggests that apoptosis aids in maintaining cellular homeostasis during the menstrual cycle by eliminating aging cells from the functional layer of the uterine endometrium. Endometriosis, which is characterized by the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. Eutopic endometrium from women with endometriosis has several differences compared with normal endometrium of women without endometriosis. These differences may contribute to the survival of regurgitated endometrial cells into the peritoneal cavity and thus to the development of endometriosis. In this article, we will summarize recent literature concerning apoptosis-related genes such as Bcl-2 and Fas, outline the molecular basis of apoptosis and review the literature focused on the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis.
Asunto(s)
Apoptosis , Endometriosis/patología , Apoptosis/genética , Apoptosis/fisiología , Caspasas/genética , Caspasas/metabolismo , Endometriosis/genética , Endometrio/química , Endometrio/patología , Epitelio/patología , Proteína Ligando Fas/análisis , Proteína Ligando Fas/genética , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-8/análisis , Interleucina-8/fisiología , Peritoneo/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/fisiología , Receptor fas/análisis , Receptor fas/genéticaRESUMEN
This study investigated the possible use of CCR1 mRNA measurement in peripheral blood leukocytes in combination with measurements of monocyte chemotactic protein-1 (MCP-1) and CA125 protein in serum as a diagnostic test for endometriosis.The expression of CCR1 mRNA in peripheral blood leukocytes was measured by quantitative real-time polymerase chain reaction. MCP-1 and CA125 levels in serum were determined by ELISA and ECLIA.The ratio of CCR1/HPRT mRNA in peripheral blood of patients with endometriosis and adenomyosis was significantly elevated compared with women without endometriosis. Additionally, serum levels of MCP-1 and CA125 were significantly higher in patients with endometriosis. This method showed a sensitivity of 92.2%, a specificity of 81.6%, a negative predictive value of 83.3%, a positive predictive value of 92.3%, a likelihood ratio of a positive test result of 5.017, and a likelihood ratio of a negative test result of 0.096 to predict the presence or absence of endometriosis.The results imply the potential use of CCR1 mRNA, MCP-1, and CA125 protein measurements for the diagnosis or exclusion of endometriosis.
Asunto(s)
Antígeno Ca-125/sangre , Quimiocina CCL2/sangre , Endometriosis/sangre , Receptores CCR1/sangre , Endometriosis/diagnóstico , Femenino , Humanos , ARN Mensajero/sangre , Receptores CCR1/genética , Estudios RetrospectivosRESUMEN
The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.
Asunto(s)
25-Hidroxivitamina D3 1-alfa-Hidroxilasa/biosíntesis , Colestanotriol 26-Monooxigenasa/biosíntesis , Neoplasias Endometriales/metabolismo , Endometriosis/metabolismo , Neoplasias Ováricas/metabolismo , Receptores de Calcitriol/biosíntesis , Esteroide Hidroxilasas/biosíntesis , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Células Cultivadas , Colestanotriol 26-Monooxigenasa/genética , Neoplasias Endometriales/enzimología , Neoplasias Endometriales/genética , Endometriosis/enzimología , Endometriosis/genética , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/genética , Receptores de Calcitriol/genética , Esteroide Hidroxilasas/genética , Vitamina D3 24-HidroxilasaRESUMEN
We investigated the expression of the cognate chemokine receptor 1 (CCR1) messenger ribonucleic acid, a G-protein-coupled cognate chemokine receptor with high affinity for RANTES (Regulated upon Activation, Normal T cells Expressed and Secreted), in peripheral blood leukocytes of women with and without endometriosis, and its potential use as a diagnostic test for endometriosis. Because patients with an earlier diagnosis of this disease have a better treatment outcome and a reduced recurrence rate, CCR1 mRNA measurement in the peripheral blood of patients with suspected endometriosis might give us a new perspective in diagnosing and treating this disease earlier and better.
Asunto(s)
Endometriosis/diagnóstico , Leucocitos/metabolismo , ARN Mensajero/sangre , Receptores de Quimiocina/genética , Antígeno Ca-125/sangre , Endometriosis/sangre , Femenino , Humanos , Embarazo , Receptores CCR1 , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To compare the amount of regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) in follicular fluid (FF) of patients with and without endometriosis and to determine their oocyte fertilization and pregnancy rates. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Germany. PATIENT(S): Thirty-two women with endometriosis stages I-IV and 28 women without endometriosis, both groups surgically and histologically confirmed. INTERVENTION(S): Diagnostic laparoscopy, IVF-ET. MAIN OUTCOME MEASURE(S): RANTES and MCP-1 levels in follicular fluid, measured by ELISA, and oocyte fertilization and pregnancy rates. RESULT(S): Follicular response and days of gonadotropin stimulation were similar between the two groups. The levels of RANTES in FF from patients with endometriosis were significantly higher (460.4 +/- 90.3 pg/mL) compared with concentrations in patients with tubal infertility (243.8 +/- 70.9 pg/mL; P<.05). In contrast, MCP-1 concentrations in FF from women with endometriosis (330.0 +/- 29.2 pg/mL) were lower than in women with tubal infertility (420.5 +/- 46.6 pg/mL; P<.05). Oocyte fertilization rates in the endometriosis group (54%) were significantly lower than those of the tubal infertility group (73%; P<.05), as were the pregnancy rates (19% vs. 35%, respectively; P<.01). CONCLUSION(S): Women with endometriosis-associated infertility have a poor IVF outcome. Immune cell recruitment into the ovary might affect follicular function and lead to impaired oocyte quality.
Asunto(s)
Quimiocina CCL2/inmunología , Quimiocina CCL5/inmunología , Endometriosis/inmunología , Fertilización In Vitro , Líquido Folicular/inmunología , Infertilidad Femenina/inmunología , Infertilidad Femenina/terapia , Adulto , Endometriosis/complicaciones , Femenino , Humanos , Infertilidad Femenina/etiología , Activación de Linfocitos/inmunología , Embarazo , Resultado del Embarazo , Linfocitos T/inmunologíaRESUMEN
Endometriosis is a pelvic inflammatory process with altered function of immune-related cells and increased number of activated macrophages in the peritoneal environment that secrete various local products, such as growth factors and cytokines. The elevation of cytokines and other factors in the peritoneal fluid is accompanied by the elevation of similar factors, such as CRP, SAA, TNF-alpha, MCP-1, IL-6, IL-8 and CCR1, in the peripheral blood of patients with endometriosis. CD44+ and CD14+ monocytes are significantly increased, while CD3+ T lymphocytes and CD20+ B lymphocytes show modest, but significant decrease in peripheral blood of women with endometriosis. This indicates that endometriosis could be viewed as a local disease with systemic subclinical manifestations. This review provides an overview of data on the changes of various factors in peripheral blood and their potential use as diagnostic tools in patients with endometriosis.