The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform

Raj K. Puri - One of the best experts on this subject based on the ideXlab platform.

  • The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not for interleukin-13–induced signal transduction through the STAT6 pathway
    Blood, 2001
    Co-Authors: Koji Kawakami, Jun Taguchi, Takashi Murata, Raj K. Puri
    Abstract:

    The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Rα1 (also known as IL-13Rα′) and IL-13Rα2 (also known as IL-13Rα). For a functional IL-13 receptor, the IL-13Rα1 chain forms a productive complex with the primary IL-4 binding Protein (IL-4Rα also known as IL-4Rβ). However, the function of the IL-13Rα2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Rα2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of 125I–IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Rα2 chain; (2) a recombinant chimeric fusion Protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Rα2–transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Rα2–transfected cells. IL-13 efficiently caused activation of STAT6 Protein in cells transfected with the IL-13Rα1 and IL-4Rα chains, and IL-13Rα2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Rα2 is signal independent and that this property of IL-13Rα2 can be exploited for receptor-directed cancer therapy.

  • the interleukin 13 receptor α2 chain an essential component for binding and internalization but not for interleukin 13 induced signal transduction through the STAT6 pathway
    Blood, 2001
    Co-Authors: Koji Kawakami, Jun Taguchi, Takashi Murata, Raj K. Puri
    Abstract:

    The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding Protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2) a recombinant chimeric fusion Protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently caused activation of STAT6 Protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Ralpha2 is signal independent and that this property of IL-13Ralpha2 can be exploited for receptor-directed cancer therapy.

Sander Kersten - One of the best experts on this subject based on the ideXlab platform.

  • activation of natural killer t cells promotes m2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin 4 il 4 STAT6 Protein signaling axis in obesity
    Journal of Biological Chemistry, 2012
    Co-Authors: Shengyi Sun, Prerna Bhargava, Liu Yang, Karen S L Lam, Bin Gao, Chihhao Lee, Sander Kersten
    Abstract:

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist α-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes.

Tanja Göck - One of the best experts on this subject based on the ideXlab platform.

  • Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 Protein
    Acta Neuropathologica, 2013
    Co-Authors: Leonille Schweizer, Christian Koelsche, Felix Sahm, Rosario M. Piro, David Capper, David E. Reuss, Stefan Pusch, Antje Habel, Jochen Meyer, Tanja Göck
    Abstract:

    Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion Protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion Protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion Protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion Protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 Proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

Koji Kawakami - One of the best experts on this subject based on the ideXlab platform.

  • The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not for interleukin-13–induced signal transduction through the STAT6 pathway
    Blood, 2001
    Co-Authors: Koji Kawakami, Jun Taguchi, Takashi Murata, Raj K. Puri
    Abstract:

    The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Rα1 (also known as IL-13Rα′) and IL-13Rα2 (also known as IL-13Rα). For a functional IL-13 receptor, the IL-13Rα1 chain forms a productive complex with the primary IL-4 binding Protein (IL-4Rα also known as IL-4Rβ). However, the function of the IL-13Rα2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Rα2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of 125I–IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Rα2 chain; (2) a recombinant chimeric fusion Protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Rα2–transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Rα2–transfected cells. IL-13 efficiently caused activation of STAT6 Protein in cells transfected with the IL-13Rα1 and IL-4Rα chains, and IL-13Rα2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Rα2 is signal independent and that this property of IL-13Rα2 can be exploited for receptor-directed cancer therapy.

  • the interleukin 13 receptor α2 chain an essential component for binding and internalization but not for interleukin 13 induced signal transduction through the STAT6 pathway
    Blood, 2001
    Co-Authors: Koji Kawakami, Jun Taguchi, Takashi Murata, Raj K. Puri
    Abstract:

    The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding Protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2) a recombinant chimeric fusion Protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently caused activation of STAT6 Protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Ralpha2 is signal independent and that this property of IL-13Ralpha2 can be exploited for receptor-directed cancer therapy.

Maximilian Woisetschlager - One of the best experts on this subject based on the ideXlab platform.

  • STAT6 mediates eotaxin 1 expression in il 4 or tnf α induced fibroblasts
    Journal of Immunology, 2001
    Co-Authors: Jutta Hoeck, Maximilian Woisetschlager
    Abstract:

    Eosinophils are attracted to sites of allergic inflammation by a number of chemoattractants including eotaxin-1. This chemokine can be secreted from epithelial cells and fibroblasts after IL-4 and TNF-α stimulation in a synergistic fashion. TNF-α activated gene expression at the transcriptional level in a STAT6-dependent manner, because: 1) eotaxin-1 promoter luciferase constructs were TNF-α inducible in STAT6-defective HEK293 cells only on cotransfection of STAT6 expression vector, an effect that was partially mediated by activation-induced binding of NF-κB Proteins to a composite STAT6/NF-κB element; 2) reporter constructs defective in STAT6 DNA binding did not respond to TNF-α stimulation; 3) eotaxin-1 Protein secretion was detected only in STAT6-transfected HEK293 cell supernatants on TNF-α treatment; and 4) a trans -dominant negative STAT6 Protein inhibited TNF-α-induced eotaxin-1 secretion in primary fibroblasts. TNF-α inducibility of the IL-8 and monocyte chemoattractant Protein-1 genes was not dependent on STAT6 expression in the same experimental systems. The inducing effect of IL-4 and IL-13 was also mediated by STAT6. The synergistic effect of IL-4 and TNF-α observed at the RNA and the Protein level was not seen at the promoter level. The data demonstrate that both IL-4 and TNF-α induce eotaxin-1 expression at the level of transcription via a STAT6-mediated pathway.