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1.
Pharmazie ; 71(4): 222-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27209704

ABSTRACT

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 > 500 µg/mL). The results justify the traditional use of the flowers of Hydnora abyssinica in South Yemen.


Subject(s)
Flowers/chemistry , Plants, Medicinal/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Bacteria/drug effects , Biphenyl Compounds/chemistry , Cell Line, Tumor , Desiccation , Drug Screening Assays, Antitumor , Ethnobotany , Free Radical Scavengers/pharmacology , Fungi/drug effects , Gas Chromatography-Mass Spectrometry , Humans , Microbial Sensitivity Tests , Picrates/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Yemen
2.
Clin Exp Immunol ; 181(1): 51-64, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25753260

ABSTRACT

In the present study we examined the role of thymic stromal lymphopoietin (TSLP) in experimental autoimmune encephalomyelitis (EAE). Here, we report that TSLP knock-out (KO) mice display a delayed onset of disease and an attenuated form of EAE. This delayed onset was accompanied by a reduced number of encephalitogenic T helper type 1 (Th1) cells in the central nervous system (CNS) of TSLP KO mice. In addition, CD4(+) and CD8(+) T cells from CNS of TSLP KO mice show a reduced activation status in comparison to wild-type mice. It is noteworthy that we could also show that lymph node cells from TSLP KO mice expanded less efficiently and that interleukin (IL)-6-, interferon (IFN)-γ and tumour necrosis factor (TNF)-α levels were reduced. Furthermore, CD3(+) T cells isolated in the preclinical phase from myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55))-immunized TSLP KO mice showed a reduced response after secondary exposure to MOG(35-55), indicating that differentiation of naive T cells into MOG(35-55)-specific effector and memory T cells was impaired in KO mice. The addition of recombinant TSLP enhanced T cell proliferation during MOG(35-55) restimulation, showing that T cells also respond directly to TSLP. In summary, these data demonstrate that expression of, and immune activation by, TSLP contributes significantly to the immunopathology of EAE.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cytokines/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Myelin-Oligodendrocyte Glycoprotein/immunology , Th1 Cells/immunology , Animals , Bone Marrow Cells/immunology , Cell Proliferation , Cells, Cultured , Central Nervous System/immunology , Cytokines/deficiency , Cytokines/genetics , Encephalomyelitis, Autoimmune, Experimental/genetics , Encephalomyelitis, Autoimmune, Experimental/pathology , Inflammation/immunology , Interferon-gamma/metabolism , Interleukin-6/metabolism , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Peptide Fragments/immunology , Th1 Cells/cytology , Tumor Necrosis Factor-alpha/metabolism , Thymic Stromal Lymphopoietin
3.
J Exp Med ; 194(12): 1813-21, 2001 Dec 17.
Article in English | MEDLINE | ID: mdl-11748282

ABSTRACT

CD83 is an immunoglobulin (Ig) superfamily member that is upregulated during the maturation of dendritic cells (DCs). It has been widely used as a marker for mature DCs, but its function is still unknown. To approach its potential functional role, we have expressed the extracellular Ig domain of human CD83 (hCD83ext) as a soluble protein. Using this tool we could show that immature as well as mature DCs bind to CD83. Since CD83 binds a ligand also expressed on immature DCs, which do not express CD83, indicates that binding is not a homophilic interaction. In addition we demonstrate that hCD83ext interferes with DC maturation downmodulating the expression of CD80 and CD83, while no phenotypical effects were observed on T cells. Finally, we show that hCD83ext inhibits DC-dependent allogeneic and peptide-specific T cell proliferation in a concentration dependent manner in vitro. This is the first report regarding functional aspects of CD83 and the binding of CD83 to DCs.


Subject(s)
Antigen Presentation , Cell Communication/immunology , Dendritic Cells/immunology , Immunoglobulins/immunology , Membrane Glycoproteins/immunology , T-Lymphocytes/immunology , Antigens, CD , Cell Differentiation/immunology , Cells, Cultured , Dendritic Cells/metabolism , Escherichia coli , Humans , Immunoglobulin Fragments/genetics , Immunoglobulin Fragments/immunology , Immunoglobulin Fragments/metabolism , Immunoglobulins/genetics , Ligands , Membrane Glycoproteins/genetics , Protein Binding/immunology , CD83 Antigen
4.
J Immunol ; 167(4): 1989-95, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11489980

ABSTRACT

Signaling lymphocyte activation molecule (SLAM), a 70-kDa costimulatory molecule that mediates CD28-independent proliferation of T cells and IFN-gamma production, has been identified on human T cells, immature thymocytes, and a subset of B cells. We have found that SLAM is expressed on mature but not immature dendritic cells (DC). However, the SLAM-associated protein, is missing in DC. SLAM surface expression is strongly up-regulated by IL-1beta. Addition of IL-1beta to the DC maturation mixture also increases the stimulatory properties of DC. These findings provide a new marker for DC maturation and help to explain two areas of DC biology. First, SLAM is a receptor for the measles virus, previously shown to infect DC. Second, SLAM could possibly contribute to the enhanced immunostimulatory functions of DC that are observed following the addition of IL-1.


Subject(s)
Dendritic Cells/immunology , Dendritic Cells/metabolism , Glycoproteins/biosynthesis , Immunoglobulins/biosynthesis , Interleukin-1/pharmacology , Lymphocyte Activation , Membrane Glycoproteins/biosynthesis , Signal Transduction/immunology , Up-Regulation/immunology , Adjuvants, Immunologic/pharmacology , Antibodies, Monoclonal/pharmacology , Antigens, CD , CD40 Antigens/immunology , Cell Differentiation/immunology , Cell Membrane/immunology , Cell Membrane/metabolism , Cells, Cultured , Dendritic Cells/cytology , Epitopes, T-Lymphocyte/immunology , Glycoproteins/analysis , Glycoproteins/genetics , Glycoproteins/immunology , Humans , Immunoglobulins/analysis , Immunoglobulins/genetics , Immunoglobulins/immunology , Intercellular Adhesion Molecule-1/biosynthesis , Lymphocyte Culture Test, Mixed , Peptides/immunology , Protein Isoforms/analysis , Protein Isoforms/genetics , RNA, Messenger/analysis , Receptors, Cell Surface , Signaling Lymphocytic Activation Molecule Family Member 1 , T-Lymphocytes, Cytotoxic/immunology , CD83 Antigen
5.
J Virol ; 74(15): 7127-36, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10888653

ABSTRACT

Mature dendritic cells (DC) are the most potent antigen-presenting cells within the entire immune system. Interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. Several members of the Herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. In this study we investigated the infection of mature DC with herpes simplex virus type 1 (HSV-1) and the way in which infection alters the phenotype and function of mature DC. Interestingly, the T-cell-stimulatory capacity of these DC was strongly impaired. Furthermore, we demonstrated that HSV-1 leads to the specific degradation of CD83, a cell surface molecule which is specifically upregulated during DC maturation. These data indicate that HSV-1 has developed yet another novel mechanism to escape immune responses.


Subject(s)
Dendritic Cells/immunology , Dendritic Cells/virology , Herpesvirus 1, Human/immunology , Lymphocyte Activation , T-Lymphocytes/immunology , Antigens, CD , Cells, Cultured , Coculture Techniques , Herpesvirus 1, Human/pathogenicity , Herpesvirus 1, Human/physiology , Humans , Immunoglobulins/metabolism , Lysosomes/metabolism , Membrane Glycoproteins/metabolism , Microscopy, Fluorescence , Phenotype , Transcription, Genetic , Virion/pathogenicity , Virion/physiology , CD83 Antigen
6.
Genes Dev ; 14(12): 1471-84, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10859166

ABSTRACT

In flowering plants, the developing embryo consists of growing populations of cells whose fates are determined in a position-dependent manner to form the adult organism. Mutations in the FACKEL (FK) gene affect body organization of the Arabidopsis seedling. We report that FK is required for cell division and expansion and is involved in proper organization of the embryo. We isolated FK by positional cloning. Expression analysis in embryos revealed that FK mRNA becomes localized to meristematic zones. FK encodes a predicted integral membrane protein related to the vertebrate lamin B receptor and sterol reductases across species, including yeast sterol C-14 reductase ERG24. We provide functional evidence that FK encodes a sterol C-14 reductase by complementation of erg24. GC/MS analysis confirmed that fk mutations lead to accumulation of intermediates in the biosynthetic pathway preceding the C-14 reductase step. Although fk represents a sterol biosynthetic mutant, the phenotype was not rescued by feeding with brassinosteroids (BRs), the only plant sterol signaling molecules known so far. We propose that synthesis of sterol signals in addition to BRs is important in mediating regulated cell growth and organization during embryonic development. Our results indicate a novel role for sterols in the embryogenesis of plants.


Subject(s)
Arabidopsis/embryology , Cell Division , Oxidoreductases/metabolism , Plant Proteins/physiology , Amino Acid Sequence , Arabidopsis/enzymology , Base Sequence , Cloning, Molecular , DNA, Complementary/metabolism , Exons , Gas Chromatography-Mass Spectrometry , Genetic Complementation Test , In Situ Hybridization , Membrane Proteins/genetics , Molecular Sequence Data , Mutation , Phenotype , Phylogeny , Plant Proteins/genetics , Polymorphism, Restriction Fragment Length , RNA, Messenger/metabolism , Signal Transduction , Time Factors , Transcription, Genetic
7.
J Exp Med ; 191(9): 1581-90, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10790432

ABSTRACT

Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N(1)-guanyl-1, 7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function.


Subject(s)
Cell Nucleus/metabolism , Dendritic Cells/cytology , Immunoglobulins/biosynthesis , Lysine/analogs & derivatives , Membrane Glycoproteins/biosynthesis , Peptide Initiation Factors/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins , Antigen Presentation/drug effects , Antigens, CD , Biological Transport/drug effects , Cell Compartmentation/drug effects , Cell Differentiation , Dendritic Cells/immunology , Guanine/analogs & derivatives , Guanine/pharmacology , Humans , Immunoglobulins/genetics , Lymphocyte Activation , Lysine/metabolism , Membrane Glycoproteins/genetics , Protein Processing, Post-Translational , T-Lymphocytes/immunology , Up-Regulation , Eukaryotic Translation Initiation Factor 5A , CD83 Antigen
9.
Zentralbl Gynakol ; 112(5): 289-92, 1990.
Article in German | MEDLINE | ID: mdl-2191532

ABSTRACT

Occasionally the intrauterine ultrasonography routinely done in the 21st gestational week pronoinced fetal ascites and intrathoracic tumour have been visualized. Spontaneous abortion of a male fetus in the 22nd gestational week. In necropsy the solid form of congenital cystic adenomatoid malformation of the whole right lung could be diagnosed.


Subject(s)
Cystic Adenomatoid Malformation of Lung, Congenital/diagnosis , Prenatal Diagnosis , Ultrasonography , Adult , Cystic Adenomatoid Malformation of Lung, Congenital/pathology , Female , Humans , Infant, Newborn , Lung/pathology , Male , Pregnancy
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