Kikumi Matsuoka

Interleukin-1β-stimulated PGE2 production from early first trimester human decidual cells is inhibited by dexamethasone and progesterone

Cytokines are known to increase the production of prostaglandins by human decidual cells, but negative regulators have not been identified. We have examined the effects of dexamethasone and progesterone on prostaglandin (PG) E2 synthesis by cultured human first trimester decidual cells. The numbers of cyclooxygenase (COX) enzyme positive cells were visualised by immunocytochemistry, using antibodies specific for COX-1 and COX-2. Interleukin-1 beta stimulated the production of prostaglandins E2 and F2 alpha dose-dependently, and this was associated with increased numbers of COX-2 positive cells. Progesterone (10(-7)-10(-6) M) and dexamethasone (10(-7)-10(-6) M) inhibited basal and interleukin-1 beta-stimulated prostaglandin production, and decreased the numbers of COX-2 positive cells. Neither interleukin-1 beta nor the steroids affected numbers of COX-1 positive cells. COX-2 seems to be the main enzyme controlling the synthesis of PGE2 by human decidual cells, and may be negatively regulated by progesterone.

Influence of α‐tumor necrosis factor and β‐interleukin‐1 on production of angiogenetic factors and thymidine phosphorylase activity in immortalized human decidual fibroblasts in vitro

Aim:  The aim of the present study was to investigate regulatory mechanisms of angiogenesis in the decidua using immortalized human decidual fibroblasts.

The effect of progesterone on genes involved in preterm labor

The decidua is known to be a major source of intrauterine PGF2α during late gestation and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well as the genes, using microarray analysis. Senescence was induced in primary cultured human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4+IL-1β decreased the expression levels of all of these genes in comparison to treatment with IL-1β alone (p<0.05). IL-1β also increased the proportion of SA-β-gal-positive cells. Treatment with IL-1β also increased the p21 protein level in comparison to cells treated either with the vehicle or P4. Neither the p21 protein level nor the number of SA-β-gal-positive cells was increased in normal endometrial glandular cells by IL-1β (p<0.05). Our studies demonstrated that P4 changes the level of gene expression in a manner that favors an anti-inflammatory milieu. Because IL-8 appears to be the cytokine whose expression is most significantly modulated by P4, further studies evaluating IL-8 as a therapeutic target are needed.

Macrophage colony-stimulating factor (M-CSF) production in vivo and in vitro in gynecologic malignancies

AbstractBackground. Macrophage colony-stimulating factor (M-CSF) secreted by malignant cells may regulate cell proliferation via an autocrine and paracrine loop, and M-CSF may be useful as a potential tumor marker. We evaluated the diagnostic significance of M-CSF levels in gynecologic patients. Methods. Serum samples were obtained from 20 healthy women and from 102 gynecologic patients undergoing primary laparotomy, and culture media were obtained from cell lines of gynecologic malignancies (oranian cancer, endometrial cancer, cervical cancer, and choriocarcinoma). M-CSF levels were measured by enzyme-linked immunosorbent assay. Results. M-CSF levels in the sera of patients with ovarian cancer and advanced uterine cancer were significantly higher than those in healthy women and in patients with benign tumors (P < 0.001). M-CSF levels 7 days after operation were significantly higher than those before operation (P < 0.001; paired t-test). But there were no differences between M-CSF levels before and after operation in patients with ovarian cancer. M-CSF levels 3 months after the cessation of treatment had decreased to within the normal range in patients with benign tumor and in cancer patients with no residual tumor. Cell lines of gynecologic malignancies produced M-CSF at various concentrations. Conclusion. These findings suggest that M-CSF, produced not only by cancer cells but also by immune cells in ascites and around tumor tissue and by connective tissue may reflect increased serum M-CSF levels in patients with ovarian cancer, advanced uterine cancer, and benign ovarian tumor, associated with ascites. It seems that operation, because of tissue damage, tissue repair, and various physiological responses, may itself, stimulate M-CSF production.

The Progression of Serum Prorenin Concentration during Pregnancy

Objective: An association between the renin-angiotensin system and the pathogenesis of pregnancy-induced hypertension has been reported. The prorenin receptor was discovered in 2002, and Wanatabe et al. reported that women with plasma soluble prorenin receptor concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia. We evaluated serum prorenin concentrations during pregnancy, and we assessed the incidence of pregnancy-induced hypertension. Methods: We measured serum prorenin concentrations in 430 pregnant women (565 samples). Regression analysis was performed to determine the associations between the serum prorenin level and maternal/neonatal complications. Results: The serum prorenin concentration and gestational age had a positive correlation in non-pregnancyinduced hypertension in women with singleton pregnancies (Spearman rank-correlation coefficient, -0.215: p<0.0001). The serum prorenin concentration in women with multiple pregnancies was significantly higher than that in women with singleton pregnancies (multiple linear regression analysis, p<0.0001). Low prorenin levels in the third trimester (≤20.1 percentile) were significantly associated with pregnancy-induced hypertension (adjusted odds ratio, 18.16: 95% confidential interval, 1.95-412.41: p=0.0107). Conclusion: The serum prorenin levels during pregnancy may be adversely correlated with the prorenin receptor, and low prorenin levels during late pregnancy were significantly associated with pregnancy-induced hypertension.

Associations between the levels of soluble (pro)renin receptor in maternal and umbilical cord blood and hypertensive disorder of pregnancy

INTRODUCTION The prorenin (PR) receptor [(P)RR] contributes to the regulation of the tissue renin-angiotensin system (RAS) and Wnt signaling, which is involved in embryogenesis and the pathological progression of malignant tumors and diabetes mellitus. Placental (P)RR is significantly upregulated in placental tissues from preeclamptic women. However, because it cannot be examined during pregnancy, the chronological relationship between the acceleration of tissue RAS and the disease state of hypertensive disorder of pregnancy (HDP) has not been reported. In this study, we examined whether chronological changes in placental tissue RAS can be assessed by measuring soluble (P)RR [s(P)RR]. METHODS We obtained maternal and umbilical cord blood samples from 517 pregnant women (441 singleton and 76 twin pregnancies). The concentrations of s(P)RR and prorenin (PR) were measured using enzyme-linked immunosorbent assays. RESULTS Multivariate analysis showed that maternal serum s(P)RR levels were significantly higher in patients with HDP or fetal growth restriction (FGR) and were positively correlated with serum PR levels. Furthermore, the maternal s(P)RR level was significantly higher in HDP with severe hypertension and after the onset of HDP. However, maternal s(P)RR levels were not affected by the severity of proteinuria. Serum s(P)RR levels in umbilical cord blood of singleton pregnancies were significantly correlated with gestational week at delivery and PR level. DISCUSSION Maternal serum s(P)RR concentrations may reflect acceleration of tissue RAS in the placenta and blood pressure severity; however, the umbilical serum s(P)RR concentration was not affected by maternal HDP.

Corrigendum to “Placental (pro)renin receptor expression and plasma soluble (pro)renin receptor levels in preeclampsia” [YPLAC 37C (2016) 72–78]

Corrigendum to “Placental (pro)renin receptor expression and plasma soluble (pro)renin receptor levels in preeclampsia” [YPLAC 37C (2016) 72e78] Tatsuya Nartita , Atsuhiro Ichihara , Kikumi Matsuoka , Yasushi Takai a, , Kanako Bokuda b, , Satoshi Morimoto , Hiroshi Itoh , Hiroyuki Seki a a Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Saitama, Japan b Department of Medicine II, Endocrinology and Hypertension, Tokyo Womens Medical University, Tokyo, Japan c Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan