TY  - JOUR
A1  - Demchuk, E.
A1  - Mueller, T.
A1  - Oschkinat, H.
A1  - Sebald, Walter
A1  - Wade, R. C.
T1  - Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis
N2  - Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4-a-helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on hormonereceptor recognition. In order to examine the specificity of hormone-receptor complexation, an analysis was made of the electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces of hGH and its receptor, and of IL-4 and its receptor, show complementary electrostatic potentials. The potentials of the hGH and its receptor display approximately 2-fold rotational symmetry because the receptor subunits are identical. In contrast, the potentials of GM-CSF and IL-2 Iack such symmetry, consistent with their known high affinity for hetero-oligomeric receptors. Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors.
KW  - Biochemie
KW  - cytokines
KW  - electrostatic potential
KW  - hematopoietic receptors
KW  - human growth factor
KW  - interleukins
KW  - molecular recognition
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62424
ER  - 
TY  - JOUR
A1  - Beyersdorf, Niklas
A1  - Werner, Sandra
A1  - Wolf, Nelli
A1  - Herrmann, Thomas
A1  - Kerkau, Thomas
T1  - Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans
JF  - PLoS One
N2  - Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8\(^+\) CD4\(^−\) αβ T cell receptor Vβ2\(^+\) CD28\(^+\) T cell lymphoma line, termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse housed under standard pathogen-free conditions. T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells.
KW  - T cells
KW  - cytotoxic T cells
KW  - mouse models
KW  - interleukins
KW  - cell staining
KW  - lymphomas
KW  - fluorescence-activated cell sorting
KW  - lymph nodes
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137946
VL  - 6
IS  - 12
ER  - 
TY  - JOUR
A1  - Alrefai, Hani
A1  - Muhammad, Khalid
A1  - Rudolf, Ronald
A1  - Pham, Duong Anh Thuy
A1  - Klein-Hessling, Stefan
A1  - Patra, Amiya K.
A1  - Avots, Andris
A1  - Bukur, Valesca
A1  - Sahin,, Ugur
A1  - Tenzer, Stefan
A1  - Goebeler, Matthias
A1  - Kerstan, Andreas
A1  - Serfling, Edgar
T1  - NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
JF  - Nature Communications
N2  - Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
KW  - B cells
KW  - psoriasis
KW  - interleukins
KW  - inflammation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173053
VL  - 7
ER  -