The Experts below are selected from a list of 376569 Experts worldwide ranked by ideXlab platform
P C Heinrich - One of the best experts on this subject based on the ideXlab platform.
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functional expression of the Interleukin 11 receptor alpha chain in normal colonic epithelium and colon cancer
International Journal of Colorectal Disease, 2006Co-Authors: Nicole Deutscher, P C Heinrich, F Bataille, Martin Hausmann, Stephan Kiessling, Gerhard Mullernewen, Sandra N Leeb, Hans H Herfarth, Jurgen Scholmerich, Gerhard RoglerAbstract:Background Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs). Activity of IL-11 requires binding to the α receptor subunit (IL-11Rα) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Rα is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Rα and its downstream signaling cascade in colonic adenoma and carcinoma.
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A fusion protein of Interleukin-11 and soluble Interleukin-11 receptor acts as a superagonist on cells expressing gp130.
FEBS Letters, 1999Co-Authors: S Pflanz, I Tacken, J Grötzinger, Y Jacques, S Minvielle, H Dahmen, P C Heinrich, G Müller-newenAbstract:Interleukin-11 is a hematopoietic cytokine that signals via the signal transducer gp130. Although gp130 is ubiquitously expressed, Interleukine-11 responsiveness is restricted to cells that express the Interleukine-11 receptor alpha-subunit. The Interleukine-11 receptor alpha-subunit can be functionally replaced by its soluble form indicating that the transmembrane and cytoplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human Interleukine-11 receptor alpha-subunit ectodomain linked to human Interleukine-11 acts as a superagonist on cells expressing gp130 but lacking the membrane-bound Interleukine-11 receptor alpha-subunit. It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells stably, transfected with gp130. In these bioassays, the fusion protein of a fragment of the human Interleukine-11 receptor alpha-subunit ectodomain linked to human Interleukine-11 is 50 times more potent than the combination of Interleukine-11 and the soluble Interleukine-11 receptor alpha-subunit. Thus, our findings support the concept that covalent fusion of two soluble proteins required for receptor activation dramatically increases their bioactivity.
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A fusion protein of Interleukin‐11 and soluble Interleukin‐11 receptor acts as a superagonist on cells expressing gp130
FEBS Letters, 1999Co-Authors: S Pflanz, I Tacken, J Grötzinger, Y Jacques, H Dahmen, P C Heinrich, G Müller-newenAbstract:Interleukin-11 is a hematopoietic cytokine that signals via the signal transducer gp130. Although gp130 is ubiquitously expressed, Interleukine-11 responsiveness is restricted to cells that express the Interleukine-11 receptor α-subunit. The Interleukine-11 receptor α-subunit can be functionally replaced by its soluble form indicating that the transmembrane and cytoplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human Interleukine-11 receptor α-subunit ectodomain linked to human Interleukine-11 acts as a superagonist on cells expressing gp130 but lacking the membrane-bound Interleukine-11 receptor α-subunit. It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells stably, transfected with gp130. In these bioassays, the fusion protein of a fragment of the human Interleukine-11 receptor α-subunit ectodomain linked to human Interleukine-11 is 50 times more potent than the combination of Interleukine-11 and the soluble Interleukine-11 receptor α-subunit. Thus, our findings support the concept that covalent fusion of two soluble proteins required for receptor activation dramatically increases their bioactivity.
Evdokia Dimitriadis - One of the best experts on this subject based on the ideXlab platform.
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leukemia inhibitory factor and Interleukin 11 critical regulators in the establishment of pregnancy
Cytokine & Growth Factor Reviews, 2009Co-Authors: Premila Paiva, Lois A Salamonsen, Ellen Menkhorst, Evdokia DimitriadisAbstract:Blastocyst implantation into a receptive endometrium is critical to the establishment of pregnancy and is tightly regulated by factors within the blastocyst–endometrial micro-environment. Leukemia inhibitory factor (LIF) and Interleukin-11 (IL11) have key roles during implantation. Female mice with a null mutation in the LIF or IL11RA gene are infertile due to a complete failure of implantation or a defective differentiation/decidualization response to the implanting blastocyst, respectively. LIF and IL11 deficiency during pregnancy is associated with infertility and miscarriage in women. Numerous cell populations at the maternal–fetal interface are regulated by LIF/IL11 including the endometrial epithelium, decidualizing stroma, placental trophoblasts and leukocytes. This review focuses on the roles of LIF/IL11 during early pregnancy and highlights their potential as contraceptive targets and therapeutic agents for infertility.
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Interleukin 11 Inhibits Human Trophoblast Invasion Indicating a Likely Role in the Decidual Restraint of Trophoblast Invasion During Placentation
Biology of Reproduction, 2009Co-Authors: Premila Paiva, Lois A Salamonsen, Ursula Chandini Manuelpillai, Evdokia DimitriadisAbstract:Successful pregnancy depends on the precise regulation of extravillous trophoblast (EVT) invasion into the uterine decidua, primarily by decidua-derived factors. In humans, during early pregnancy Interleukin 11 (IL11) is maximally expressed in the decidua, with its receptor, IL11 receptor alpha (IL11RA), also identified on invasive EVTs in vivo. Although a role for IL11 in EVT migration has been established, whether it also plays a role in regulating EVT invasion is unknown. We investigated whether IL11 influences human EVT invasion and the signaling pathways and underlying mechanisms that may be involved, using the HTR-8/SVneo immortalized EVT cell line and primary EVTs as models for EVTs. Interleukin 11 (100 ng/ml) significantly inhibited invasion of EVT cells by 40% to 60% (P < 0.001). This effect was abolished by inhibitors of signal transducer and activator of transcription 3 (STAT3) but not of mitogen-activated protein kinase (MAPK) pathways. Interleukin 11 (100 ng/ml) had no effect on matrix metallopeptidases 2 and 9 (MMP2 and MMP9), tissue inhibitors of MMP (TIMP1, TIMP2, and TIMP3), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and serpin peptidase inhibitors 1 and 2 (SERPINE1 and SERPINE2) in EVT-conditioned media and/or cell lysates. Interleukin 11 (100 ng/ml) also did not regulate EVT cell adhesion or integrin expression. These data demonstrate that IL11 inhibits human EVT invasion via STAT3, indicating a likely role for IL11 in the decidual restraint of EVT invasion during normal pregnancy.
Gerhard Rogler - One of the best experts on this subject based on the ideXlab platform.
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functional expression of the Interleukin 11 receptor alpha chain in normal colonic epithelium and colon cancer
International Journal of Colorectal Disease, 2006Co-Authors: Nicole Deutscher, P C Heinrich, F Bataille, Martin Hausmann, Stephan Kiessling, Gerhard Mullernewen, Sandra N Leeb, Hans H Herfarth, Jurgen Scholmerich, Gerhard RoglerAbstract:Background Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs). Activity of IL-11 requires binding to the α receptor subunit (IL-11Rα) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Rα is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Rα and its downstream signaling cascade in colonic adenoma and carcinoma.
G Müller-newen - One of the best experts on this subject based on the ideXlab platform.
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A fusion protein of Interleukin-11 and soluble Interleukin-11 receptor acts as a superagonist on cells expressing gp130.
FEBS Letters, 1999Co-Authors: S Pflanz, I Tacken, J Grötzinger, Y Jacques, S Minvielle, H Dahmen, P C Heinrich, G Müller-newenAbstract:Interleukin-11 is a hematopoietic cytokine that signals via the signal transducer gp130. Although gp130 is ubiquitously expressed, Interleukine-11 responsiveness is restricted to cells that express the Interleukine-11 receptor alpha-subunit. The Interleukine-11 receptor alpha-subunit can be functionally replaced by its soluble form indicating that the transmembrane and cytoplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human Interleukine-11 receptor alpha-subunit ectodomain linked to human Interleukine-11 acts as a superagonist on cells expressing gp130 but lacking the membrane-bound Interleukine-11 receptor alpha-subunit. It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells stably, transfected with gp130. In these bioassays, the fusion protein of a fragment of the human Interleukine-11 receptor alpha-subunit ectodomain linked to human Interleukine-11 is 50 times more potent than the combination of Interleukine-11 and the soluble Interleukine-11 receptor alpha-subunit. Thus, our findings support the concept that covalent fusion of two soluble proteins required for receptor activation dramatically increases their bioactivity.
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A fusion protein of Interleukin‐11 and soluble Interleukin‐11 receptor acts as a superagonist on cells expressing gp130
FEBS Letters, 1999Co-Authors: S Pflanz, I Tacken, J Grötzinger, Y Jacques, H Dahmen, P C Heinrich, G Müller-newenAbstract:Interleukin-11 is a hematopoietic cytokine that signals via the signal transducer gp130. Although gp130 is ubiquitously expressed, Interleukine-11 responsiveness is restricted to cells that express the Interleukine-11 receptor α-subunit. The Interleukine-11 receptor α-subunit can be functionally replaced by its soluble form indicating that the transmembrane and cytoplasmic parts are not required for signal transduction. Here, we show that a recombinant fusion protein of a fragment of the human Interleukine-11 receptor α-subunit ectodomain linked to human Interleukine-11 acts as a superagonist on cells expressing gp130 but lacking the membrane-bound Interleukine-11 receptor α-subunit. It induces acute phase protein synthesis in hepatoma cells and efficiently promotes proliferation of Ba/F3 cells stably, transfected with gp130. In these bioassays, the fusion protein of a fragment of the human Interleukine-11 receptor α-subunit ectodomain linked to human Interleukine-11 is 50 times more potent than the combination of Interleukine-11 and the soluble Interleukine-11 receptor α-subunit. Thus, our findings support the concept that covalent fusion of two soluble proteins required for receptor activation dramatically increases their bioactivity.
Premila Paiva - One of the best experts on this subject based on the ideXlab platform.
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leukemia inhibitory factor and Interleukin 11 critical regulators in the establishment of pregnancy
Cytokine & Growth Factor Reviews, 2009Co-Authors: Premila Paiva, Lois A Salamonsen, Ellen Menkhorst, Evdokia DimitriadisAbstract:Blastocyst implantation into a receptive endometrium is critical to the establishment of pregnancy and is tightly regulated by factors within the blastocyst–endometrial micro-environment. Leukemia inhibitory factor (LIF) and Interleukin-11 (IL11) have key roles during implantation. Female mice with a null mutation in the LIF or IL11RA gene are infertile due to a complete failure of implantation or a defective differentiation/decidualization response to the implanting blastocyst, respectively. LIF and IL11 deficiency during pregnancy is associated with infertility and miscarriage in women. Numerous cell populations at the maternal–fetal interface are regulated by LIF/IL11 including the endometrial epithelium, decidualizing stroma, placental trophoblasts and leukocytes. This review focuses on the roles of LIF/IL11 during early pregnancy and highlights their potential as contraceptive targets and therapeutic agents for infertility.
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Interleukin 11 Inhibits Human Trophoblast Invasion Indicating a Likely Role in the Decidual Restraint of Trophoblast Invasion During Placentation
Biology of Reproduction, 2009Co-Authors: Premila Paiva, Lois A Salamonsen, Ursula Chandini Manuelpillai, Evdokia DimitriadisAbstract:Successful pregnancy depends on the precise regulation of extravillous trophoblast (EVT) invasion into the uterine decidua, primarily by decidua-derived factors. In humans, during early pregnancy Interleukin 11 (IL11) is maximally expressed in the decidua, with its receptor, IL11 receptor alpha (IL11RA), also identified on invasive EVTs in vivo. Although a role for IL11 in EVT migration has been established, whether it also plays a role in regulating EVT invasion is unknown. We investigated whether IL11 influences human EVT invasion and the signaling pathways and underlying mechanisms that may be involved, using the HTR-8/SVneo immortalized EVT cell line and primary EVTs as models for EVTs. Interleukin 11 (100 ng/ml) significantly inhibited invasion of EVT cells by 40% to 60% (P < 0.001). This effect was abolished by inhibitors of signal transducer and activator of transcription 3 (STAT3) but not of mitogen-activated protein kinase (MAPK) pathways. Interleukin 11 (100 ng/ml) had no effect on matrix metallopeptidases 2 and 9 (MMP2 and MMP9), tissue inhibitors of MMP (TIMP1, TIMP2, and TIMP3), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and serpin peptidase inhibitors 1 and 2 (SERPINE1 and SERPINE2) in EVT-conditioned media and/or cell lysates. Interleukin 11 (100 ng/ml) also did not regulate EVT cell adhesion or integrin expression. These data demonstrate that IL11 inhibits human EVT invasion via STAT3, indicating a likely role for IL11 in the decidual restraint of EVT invasion during normal pregnancy.