19 research outputs found

    Pro- and anti-inflammatory cytokines in threatened miscarriages

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    OBJECTIVE: The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatenedmiscarriage (TM) and subsequent outcome. STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF , interferon gamma (IFN ), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS: Monocyte expression of TNF and circulating levels of TNF , IFN , IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF /IL-10, IFN /IL-10, and TNF /IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage.peer-reviewe

    Investigation of systemic inflammatory response in first trimester pregnancy failure

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    Background: The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage. Methods: Levels of tumour necrosis factor alpha (TNFa), TNF receptors 1 and 2, interferon gamma (IFNg), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW. Results: The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNFa (P , 0.005), IFNg (P , 0.005), IL-6 (P , 0.005) and IL-10 (P , 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P , 0.05) higher TNF-R1 levels at 6–9 weeks, and significantly higher TNFa/IL-6 (P , 0.001) and significantly lower TNFa/IL-10 (P , 0.001) and IFNg/IL-10 (P , 0.001) ratios at 10–14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNFa/IL-10 ratio in plasma was significantly (P , 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFNg (P , 0.01) and IFNg/IL-10 ratio (P , 0.005), a significantly (P , 0.005) lower TNF-R1 level, and a significant (P , 0.05) increase in stimulated TNFa in monocytes, compared with NPW. Conclusions: Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.peer-reviewe

    Pro-and antiinflammatory cytokines in threatened miscarriages

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    OBJECTIVE: The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatened miscarriage (TM) and subsequent outcome. STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF␣, interferon gamma (IFN␥), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS: Monocyte expression of TNF␣ and circulating levels of TNF␣, IFN␥, IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF␣/IL-10, IFN␥/IL-10, and TNF␣/IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage

    KSHV Manipulates Notch Signaling by DLL4 and JAG1 to Alter Cell Cycle Genes in Lymphatic Endothelia

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    Increased expression of Notch signaling pathway components is observed in Kaposi sarcoma (KS), but the mechanism underlying the manipulation of the canonical Notch pathway by the causative agent of KS, Kaposi sarcoma herpesvirus (KSHV), has not been fully elucidated. Here, we describe the mechanism through which KSHV directly modulates the expression of the Notch ligands JAG1 and DLL4 in lymphatic endothelial cells. Expression of KSHV-encoded vFLIP induces JAG1 through an NF kappa B-dependent mechanism, while vGPCR upregulates DLL4 through a mechanism dependent on ERK. Both vFLIP and vGPCR instigate functional Notch signalling through NOTCH4. Gene expression profiling showed that JAG1- or DLL4-stimulated signaling results in the suppression of genes associated with the cell cycle in adjacent lymphatic endothelial cells, indicating a role for Notch signaling in inducing cellular quiescence in these cells. Upregulation of JAG1 and DLL4 by KSHV could therefore alter the expression of cell cycle components in neighbouring uninfected cells during latent and lytic phases of viral infection, influencing cellular quiescence and plasticity. In addition, differences in signaling potency between these ligands suggest a possible complementary role for JAG1 and DLL4 in the context of KS

    Degranulation of individual mast cells in response to Ca 2� and guanine nucleotides: an all-or-none event

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    Abstract. Widespread experience indicates that application of suboptimal concentrations of stimulating ligands (secretagogues) to secretory cells elicits submaximal extents of secretion. Similarly, for permeabilized secretory cells, the extent of secretion is related to the concentration of applied intracellular effectors. We investigated the relationship between the extent of secretion from mast cells (assessed as the release of hexosaminidase) and the degranulation (exocytosis) responses of individual cells. For permeabilized mast cells stimulated by the effector combination Ca 2+ plus GTP-3,-S and for intact cells stimulated by the Ca 2÷ ionophore ionomycin, we found that exocytosis has the characteristics of an all-or-none process at the level of the individual cell. With a suboptimal stimulus, th
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