7 results on '"Solari R"'
Search Results
2. Analysis of structure/activity relationship of interleukin 5 (IL5) by site directed mutagenesis
- Author
-
McKinnon, M, Banks, M., Fattah, D, and Solari, R
- Published
- 1994
- Full Text
- View/download PDF
3. A rapid activation assay for human eosinophils based on adhesion to immobilized ICAM-1, VCAM-1 and IgG.
- Author
-
Fattah D, Page KR, Bezbaruah S, Priest RC, Horgan CM, and Solari R
- Subjects
- Animals, Antibodies, Monoclonal, Antigens, CD analysis, Cell Adhesion, Cells, Cultured, Cytoplasmic Granules drug effects, Cytoplasmic Granules physiology, Eosinophils cytology, Eosinophils drug effects, Flow Cytometry, Humans, Interleukin-5 pharmacology, Kinetics, L-Selectin analysis, Mice, Recombinant Proteins pharmacology, Vascular Cell Adhesion Molecule-1, Cells, Immobilized, Chemokines pharmacology, Cytokines pharmacology, Eosinophils physiology, Immunoglobulin G, Intercellular Adhesion Molecule-1
- Abstract
Interleukin 5 (IL-5) is a T-cell derived cytokine that induces eosinophil growth and differentiation in both mouse and human bone marrow cultures. Elevated levels of IL-5 as well as eosinophils have been detected in the sputum and Bronchoalveolar lavage (BAL) fluids of asthmatics. Since the recruitment of inflammatory cells to tissues requires the participation of adhesion molecules, we have developed a rapid and sensitive assay to examine the effect of IL-5 and other activation stimuli on eosinophil adhesion to recombinant intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Human recombinant IL-5, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), tumour necrosis factor alpha (TNF-alpha), RANTES, MCP-3, C5a, PAF, fMLP, PMA and ConA all induced adhesion of purified eosinophils obtained from normal donors to ICAM-1 and VCAM-1 in a dose and time dependent manner. Adhesion was rapid, within 15 minutes of culture at 37 degrees C, and plateaued within 30 minutes. Activated eosinophils also adhered rapidly to immobilized IgG via the type II Fc gamma receptor (CD32). Analysis of the effect of IL-5 on surface molecule expression by FACS analysis revealed increased expression of CD11b molecules and decreased expression of L-selectin, but no change in the expression of CD11a, CD18, CD29, CD49d and CD32. We also show that Mac-i plays an important role in the regulation of eosinophil activation, since antibodies to CD11b can block IL-5 induced adhesion to IgG and IL-5 induced degranulation.
- Published
- 1996
- Full Text
- View/download PDF
4. Acute upregulation of interleukin-1 receptor by ligand.
- Author
-
Grenfell SJ, Smithers N, and Solari R
- Subjects
- Animals, Receptors, Interleukin-1, Tumor Cells, Cultured, Up-Regulation drug effects, Endocytosis drug effects, Interleukin-1 pharmacology, Receptors, Immunologic drug effects
- Abstract
In this study we have investigated the effect that interleukin 1 (IL-1) has on cell surface IL-1 receptor expression in the murine thymoma cell line, EL4 6.1. These cells express IL-1 receptors with both high affinity (Kd = 65 pM, 986 receptors/cell) and low affinity (Kd = 14.5 nM, 10,417 receptors/cell). The high- and low-affinity receptors are indistinguishable by crosslinking studies performed at both high and low ligand concentrations. However, the two affinity states could be functionally distinguished on the basis of their internalization of ligand. Receptor-mediated endocytosis was dependent upon the concentration of ligand bound to the cells. In the presence of low IL-1 concentrations receptor-mediated endocytosis was slow, whereas at high IL-1 concentrations, endocytosis was more rapid. Furthermore, receptor-mediated endocytosis of IL-1 did not result in downregulation of surface IL-1 receptors. Indeed, both kinetic and equilibrium binding studies revealed that pre-incubation of cells with IL-1 alpha resulted in an acute upregulation of 125IL-1 alpha binding to high affinity surface receptors in a time and energy dependent manner. Examination of the association kinetics suggested that increased binding was not attributable to positive co-operativity of the high affinity IL-1 receptor, but was due to increasing IL-1 receptor number. This observation was confirmed by equilibrium binding studies. Moreover, receptor numbers were not enhanced by de novo synthesis, nor release of receptors from an intracellular pool. The observed increases in surface ligand binding were most probably due to conversion of the surface pool of low affinity receptors into high affinity receptors.
- Published
- 1992
- Full Text
- View/download PDF
5. Cloning and chromosome mapping of the human interleukin-1 receptor antagonist gene.
- Author
-
Lennard A, Gorman P, Carrier M, Griffiths S, Scotney H, Sheer D, and Solari R
- Subjects
- Amino Acid Sequence, Base Sequence, Fluorescence, Genomic Library, Humans, Interleukin 1 Receptor Antagonist Protein, Molecular Sequence Data, Nucleic Acid Hybridization, Recombinant Proteins genetics, Cloning, Molecular, Proteins genetics, Restriction Mapping, Sialoglycoproteins
- Abstract
By screening a human genomic library with an interleukin-1 receptor antagonist (IL-1ra) cDNA probe, we have isolated a 15 kb clone which contains the entire coding region of the gene as expressed in monocytes, and includes 6 kb of 5'-upstream sequence. The gene contains four exons which code for the secreted form of the IL-1ra, however, our clone does not contain the alternative first exon used to generate an intracellular form of the protein as the protein as found in epithelial cells. Analysis of the sequence reveals a consensus TATA box, and three Alu repeats, two of which are in the upstream region and one in intron 3. The sequence also reveals an 86 bp motif tandomly repeated four times within intron 2, and may reflect the polymorphism known to exist in this region of the gene. By in-situ fluorescence hybridization we have shown that the IL-1ra gene is found on the long arm of chromosome 2 and maps to 2q13-14.1. Previous studies have revealed that IL-1 alpha, and IL-1 beta and both type I and type II forms of the IL-1 receptor all map close to this region of chromosome 2.
- Published
- 1992
- Full Text
- View/download PDF
6. Modification of biological responses to interleukin-1 by agents that perturb signal transduction pathways.
- Author
-
Rollins P, Witham S, Ray K, Thompson N, Sadler H, Smithers N, Grenfell S, and Solari R
- Subjects
- 1-Methyl-3-isobutylxanthine pharmacology, 8-Bromo Cyclic Adenosine Monophosphate pharmacology, Animals, Cell Division drug effects, Cell Line, Cholera Toxin pharmacology, Colforsin pharmacology, Cyclic AMP physiology, Diglycerides pharmacology, Dinoprostone metabolism, Flow Cytometry, Interleukin-2 biosynthesis, Interleukin-2 pharmacology, Lymphocyte Activation, Mice, Pertussis Toxin, Protein Kinase C metabolism, Recombinant Proteins pharmacology, T-Lymphocytes, Cytotoxic immunology, Tetradecanoylphorbol Acetate pharmacology, Virulence Factors, Bordetella pharmacology, Interleukin-1 pharmacology, Signal Transduction drug effects
- Abstract
In this study we have examined the effect of agents known to perturb certain signal transduction pathways on the biological responses of target cells to stimulation with interleukin-1 (IL-1). In the murine thymoma cell line EL4, IL-1 stimulation results in the secretion of interleukin-2 (IL-2), which was subsequently measured by proliferation of an IL-2-dependent cell line. Agents that elevated intracellular cAMP blocked or partially blocked IL-1 induction of IL-2 secretion, whereas agents that activated protein kinase C (PKC) resulted in a synergistic enhancement. Both pertussis and cholera toxins also inhibited IL-1-induced IL-2 secretion, although probably by acting at different levels. IL-1 simulation of human and murine fibroblasts resulted in release of prostaglandin E2. This response was inhibitable by pertussis toxin but not by cholera toxin, whereas co-stimulation of the fibroblasts with IL-1 and phorbol ester resulted in a synergistic response. Murine fibroblasts could also be stimulated to proliferate by IL-1, and this response was also inhibitable by pertussis toxin. These findings are consistent with coupling of the IL-1 receptor to a signalling pathway via a pertussis toxin substrate.
- Published
- 1991
- Full Text
- View/download PDF
7. Interleukin 1 responsiveness and receptor expression by murine TH1 and TH2 clones.
- Author
-
Solari R, Smithers N, Page K, Bolton E, and Champion BR
- Subjects
- Animals, Antigens, Differentiation, T-Lymphocyte physiology, CD3 Complex, Cell Division drug effects, Clone Cells, Concanavalin A pharmacology, Cross-Linking Reagents chemistry, Dose-Response Relationship, Drug, Interleukin-2 pharmacology, Interleukin-4 pharmacology, Lymphocyte Activation drug effects, Mice, Molecular Weight, Receptors, Antigen, T-Cell physiology, Receptors, Immunologic chemistry, Receptors, Interleukin-1, CD4-Positive T-Lymphocytes physiology, Interleukin-1 pharmacology, Receptors, Immunologic physiology, T-Lymphocytes, Helper-Inducer physiology
- Abstract
Murine Th1 and Th2 T cell lines differ in their responses to interleukin 1 (IL 1). Therefore, we examined two T-cell lines, D10.G4.1 (Th2) and MTg12B (Th1) in an attempt to correlate IL 1 receptor (IL 1R) expression with their IL 1 responsiveness. D10.G4.1 cells, which respond to IL 1, expressed two forms of the IL 1R, with molecular masses of approximately 80 kDa and approximately 60 kDa. In contrast, MTg12B cells failed to respond to IL 1 and only expressed the approximately 60 kDa receptor form. This suggests that the approximately 80 kDa receptor is essential for signaling. Expression of both IL 1R forms on D10.G4.1 cells could be inhibited by the anti-IL 4 antibody, 11B11. Antigen presentation reversibly upregulated both forms of the IL 1R, whereas stimulation with concanavalin A (ConA) and anti-CD3 only upregulated the approximately 60 kDa moiety. Upregulation of the approximately 80-kDa IL 1R by repeated antigenic stimulation resulted in a marked increase in sensitivity of D10.G4.1 cells to IL 1.
- Published
- 1990
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.