The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Kiyoshi Takatsu - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the identification and cDNA cloning of T cell-replacing factor/Interleukin-5.
Frontiers in immunology, 2014Co-Authors: Kiyoshi TakatsuAbstract:This is a perspective based on the paper "Cloning of complementary DNA encoding T cell replacing factor and identity with B cell growth factor II", by Kinashi T, Harada N, Severinson E, Tanabe T, Sideras P, Konishi M, Azuma C, Tominaga A, Bergstedt-Lindqvist S, Takahashi M, Matsuda F, Yaoita Y, Takatsu K, and Honjo, T. Nature (1986) 32(6092): 70-3. We have been interested in understanding the molecular basis of T-B cell cooperation for antibody formation. Although many investigators had described a number of different soluble factors that appeared to have biological relevance to T-B cell interactions, molecular basis of such active substances remained unknown for a long period of time. In this perspective, I will briefly summarize the history of the initial discovery of T cell-replacing factor/B cell growth factor II that appeared to be involved in B-cell growth and differentiation, and outline the discovery and characterization of Interleukin-5. Studies of Interleukin-5 have provided strong evidence that a single cytokine exerts a variety of activities on diverse target cells.
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Interleukin 5 and B cell differentiation
Cytokine & growth factor reviews, 1998Co-Authors: Kiyoshi TakatsuAbstract:Abstract Interleukin-5 (IL-5) stimulates proliferation and differentiation of B cells and eosinophils. IL-5 receptor (IL-5R) comprises α and β c chains. IL-5 specifically binds to IL-5R α and induces the recruitment of β c to IL-5R α . JAK2 and JAK1 tyrosine kinases are constitutively associated with hIL-5R α and β c, respectively and activated upon IL-5 stimulation. IL-5 induces tyrosine phosphorylations of cellular proteins including β c and STAT5 and activates Btk. X-linked immunodeficient mice have B-cell-specific defects due to missense mutation of the btk gene. The cytoplasmic proline-rich regions of both IL-5R α and β c are essential for the IL-5 signalling. IL-5 appears to play a critical role in hypereosinophilic syndromes and atopic diseases. The treatment of animals with anti-IL-5 mAb can decrease the enhanced bronchial responsiveness induced by allergen sensitization. Clinical studies provide a strong impetus for investigating the means of modulating IL-5 effects.
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Interleukin-5
BioDrugs, 1997Co-Authors: Kiyoshi TakatsuAbstract:Interleukin-5 (IL-5) is an interdigitating homodimeric glycoprotein and features the 4-α-helical-bundle motif which is conserved among several haemopoietic cytokines. It is a potent cytokine which induces proliferation and differentiation of activated B cells and induces eosinophil production and activation. IL-5 acts on target cells by binding to its specific receptor. The IL-5 receptor consists of a unique α chain and a β (βc) chain that is shared with the receptors for Interleukin-3 and granulocyte-macrophage colony-stimulating factor. The βc chain is indispensable for signal transduction. Both subunits contain motifs conserved among the superfamily of cytokine receptors. Stimulation of cells by IL-5 induces rapid tyrosine phosphorylation of various cellular proteins, including the βc chain, and activates the Bruton tyrosine (Btk) and JAK2 kinases. The cytoplasmic domain of the βc chain and the membrane-proximal proline-rich sequence of the cytoplasmic domain of the α chain are both essential for the IL-5-induced proliferative response, for expression of nuclear proto-oncogenes and for activation of the Btk and JAK2 kinases. B cells from X-linked immunodeficient (XID) mice, which have an abnormality of Btk and lack functionally mature B cells, including CD5+ B cells, show impaired responsiveness to IL-5, whereas eosinophils from these animals respond normally. In several pathophysiological conditions, increases in serum and tissue levels of IL-5 and eosinophil numbers have been described. Of clinical relevance is a role for IL-5 in hypereosinophilic syndromes and atopic disease. An animal model of local allergen (airways) sensitisation was employed to study the effects of anti-IL-5 monoclonal antibody on infiltration of eosinophils into inflammatory regions and the development of the antigen-induced late-phase asthmatic response and subsequent bronchial responsiveness. Treatment with the anti-IL-5 antibody decreased the enhanced bronchial responsiveness to acetylcholine induced by allergen sensitisation via the airways. These diverse biological consequences of IL-5 provide the basis for elucidating the functional structure of IL-5 and its receptor complex, as well as the mechanisms of IL-5 signal transduction. Furthermore, clinical studies provide insight into the role of IL-5 in health and disease and provide a strong impetus for investigating means of modulating the effects of IL-5. In concert with advances in understanding the biology of other cytokines and growth factors, entirely new approaches to patient care should emerge in the near future.
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Interleukin-5: an overview.
Cancer treatment and research, 1995Co-Authors: Kiyoshi TakatsuAbstract:Interleukin 5 (IL-5) is a cytokine mainly produced by activated T cells upon stimulation with antigen, and by mast cells upon stimulation with allergen/IgE complex or calcium ionophores [1,2]. The study of murine (m) IL-5 originated in the search for T-cell-replacing factor (TRF), which induces 2,4-dinitrophenyl (DNP)-primed B cells to differentiate into anti-DNP IgG-producing cells [3], as well as the proliferation of BCL1 B-cell tumor cells into IgM-secreting cells (B-cell differentiation factor-μ, BCDFμ) [4,5]. IL-5 also regulates the proliferation of activated B cells (B-cell growth factor II, BCGFII) [6], and enhances IgA synthesis (IgA-enhancing factor, IgA-EF) [7–10] and functions of eosinophils and basophils (eosinophil-differentiation factor, EDF) [11]. Thus IL-5 is a synonym of TRF, BCDFμ, BCGFII, IgA-EF and EDF. A number of mIL-5-dependent mouse B-cell lines have now been isolated and provide a convenient biological assay for IL-5 [12]. In humans, human (h) IL-5 inducs the production of eosinophils from bone marrow progenitors and works for survival and priming of eosinophils in vitro [11]. hIL-5 expression was observed in many diseases with eosinophilia, suggesting that IL-5 plays important roles in promoting the production and function of eosinophils in vivo.
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Evaluation of airway hyperreactivity in Interleukin-5 transgenic mice.
International Archives of Allergy and Immunology, 1995Co-Authors: Teiji Iwamoto, Kiyoshi TakatsuAbstract:Interleukin-5 (IL-5) transgenic mice constitutively produce IL-5 and show massive eosinophilia in peripheral blood as well as infiltration of eosinophils into various tissues. This study investigated whether airway hyperreactivity occurs in the airways of IL-5 transgenic mice. These mice showed marked eosinophilia in bronchoalveolar lavage fluid, but no increase in reactivity to acetylcholine. IL-5 transgenic mice actively sensitized with ovalbumin displayed more profound airway hyperreactivity in response to acetylcholine 24 h after inhalation challenge with ovalbumin. Wild-type mice treated the same way showed little, if any, airway hyperreactivity. These findings indicate that this mouse model of airway hyperreactivity is useful in understanding the mechanism underlying pulmonary eosinophilia and the consequent inflammation.
Colin J. Sanderson - One of the best experts on this subject based on the ideXlab platform.
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Dexamethasone suppresses human Interleukin-5 gene promoter.
Bulletin of experimental biology and medicine, 2005Co-Authors: Viatcheslav A. Mordvinov, Chee Choy Kok, Estri Arthaningtyas, Gretchen T F Schwenger, A. Cristow, Colin J. SandersonAbstract:Synthetic glucocorticoid dexamethasone suppressed Interleukin-5 gene expression in PER-117 human T cells at the level of transcription. The conserved lymphokine element 0 in the Interleukin-5 gene promoter context served as a target for dexamethasone.
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The Cytokine Handbook (Fourth Edition) - CHAPTER 11 – Interleukin-5
The Cytokine Handbook, 2003Co-Authors: Chee Choy Kok, Gretchen T F Schwenger, Ron I.w. Osmond, Debra L. Urwin, Colin J. SandersonAbstract:This chapter deals with Interleukin-5, which is the highly conserved member of a group of evolutionary related cytokines which are associated with eosinophilia. It plays an essential role in promoting growth, differentiation, survival, and activation of eosinophils. Thus, it is important to understand the mechanisms of IL-5 regulation, and its activities on eosinophils. To date, most studies have focused on the regulation of the IL-5 gene. While many findings have been made, the complete mechanism of IL-5 regulation has yet to be understood. More studies on the IL-5 gene, protein, and receptor are needed to provide a better understanding of its functions and how it may be specifically regulated for the therapeutic purposes.
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New directions in understanding Interleukin-5 gene expression
Leukemia & lymphoma, 1998Co-Authors: Gretchen T F Schwenger, Colin J. SandersonAbstract:Specific regulation of the Interleukin-5 (IL-5) gene is implied by the unique control of eosinophilia which is regulated by IL-5. In studies of IL-5 gene expression, the only control elements identified for the IL-5 gene have been transcriptional elements in the 5' untranslated region (UTR). Significant differences exist in the arrangement of the murine and human IL-5 promoters, which is surprising considering the tight regulation of the gene. Novel palindromic regulatory elements involved in transcriptional regulation have been found in the 5' UTR and new results show the presence of transcriptional elements in the 3' UTR. Post-transcriptional control mechanisms in both the 5' and 3' UTRs have also been described.
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Biological and Molecular Characteristics of Interleukin-5 and its Receptor
International reviews of immunology, 1998Co-Authors: Stéphane Karlen, M. L. De Boer, R. J. Lipscombe, W. Lutz, V. A. Mordvinov, Colin J. SandersonAbstract:Interleukin-5 (IL5) is a T cell-derived cytokine involved in the pathogenesis of atopic diseases. It specifically controls the production, the activation and the localization of Eosinophils. The Eosinophils are the major cause of tissue damage resulting in the symptoms of asthma and related allergic disorders. T cells purified from bronchoalveolar lavage and peripheral blood of asthmatics secrete elevated amount of IL5. Therefore IL5 emerges to be an attractive target for the generation of new antiallergic drugs. Agents which inhibit either the production or the activity of IL5 could be expected to ameliorate the pathological effects of the allergic response. A better understanding of the biology of IL5 and the regulation of its expression is, however, a prerequisite for the development of new therapeutic agents. This review covers the major biological, molecular and structural aspects of IL5 research since the identification of this cytokine ten years ago.
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Anti-Interleukin 5 strategies as a potential treatment for asthma.
Thorax, 1997Co-Authors: Anish D Singh, Colin J. SandersonAbstract:A paradigm shift, championed largely by cellular immunologists, has redefined asthma as an immune mediated phenomenon characterised by an Interleukin 5 (IL-5) driven eosinophilic bronchitis. This change in emphasis has provoked intense interest in the possibility that inhibitors of IL-5 production, or antagonists of its activity, will provide a new generation of anti-asthma drugs.
Frans P. Nijkamp - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs.
European journal of pharmacology, 1993Co-Authors: Antoon J.m. Van Oosterhout, Ingrid Van Ark, Gerard A. Hofman, Huub F. J. Savelkoul, Frans P. NijkampAbstract:Abstract Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 × 106/animal). These cells produced approximately 8 ng Interleukin-5 per 4 × 106 cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in Interleukin-5-treated animals. In animals treated with antibody to Interleukin-5, the administration of Interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not a 3 days after administration of Interleukin-5-producing CV-1 cells. Antibody to Interleukin-5 prevented the broncho-alveolar lavage eosunophilia at 7 days after Interleukin-5 administration. It can be concluded that Interleukin-5 induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for Interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma.
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Recombinant Interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs: European journal of pharmacology, 236 (1993) 379–383
European Journal of Pharmacology, 1993Co-Authors: Antoon J.m. Van Oosterhout, Ingrid Van Ark, Gerard A. Hofman, Huub F. J. Savelkoul, Frans P. NijkampAbstract:Abstract Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 × 10 6 /animal). These cells produced approximately 8 ng Interleukin-5 per 4 × 10 6 cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in Interleukin-5-treated animals. In animals treated with antibody to Interleukin-5, the administration of Interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not at 3 days after administration of Interleukin-5-producing CV-1 cells. Antibody to Interleukin-5 prevented the broncho-alveolar lavage eosinophilia at 7 days after Interleukin-5 administration. It can be concluded that Interleukin-5- induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for Interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma.
Antoon J.m. Van Oosterhout - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs.
European journal of pharmacology, 1993Co-Authors: Antoon J.m. Van Oosterhout, Ingrid Van Ark, Gerard A. Hofman, Huub F. J. Savelkoul, Frans P. NijkampAbstract:Abstract Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 × 106/animal). These cells produced approximately 8 ng Interleukin-5 per 4 × 106 cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in Interleukin-5-treated animals. In animals treated with antibody to Interleukin-5, the administration of Interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not a 3 days after administration of Interleukin-5-producing CV-1 cells. Antibody to Interleukin-5 prevented the broncho-alveolar lavage eosunophilia at 7 days after Interleukin-5 administration. It can be concluded that Interleukin-5 induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for Interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma.
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Recombinant Interleukin-5 induces in vivo airway hyperresponsiveness to histamine in guinea pigs: European journal of pharmacology, 236 (1993) 379–383
European Journal of Pharmacology, 1993Co-Authors: Antoon J.m. Van Oosterhout, Ingrid Van Ark, Gerard A. Hofman, Huub F. J. Savelkoul, Frans P. NijkampAbstract:Abstract Interleukin-5-producing CV-1 cells were encapsulated in alginate and injected i.p. in guinea pigs (4 × 10 6 /animal). These cells produced approximately 8 ng Interleukin-5 per 4 × 10 6 cells per day. Airway hyperresponsiveness to histamine in vivo was observed 3 and 7 days after administration. The increase in lung resistance after intravenous administration of histamine to guinea pigs was significantly potentiated, by approximately 70 to 90% in Interleukin-5-treated animals. In animals treated with antibody to Interleukin-5, the administration of Interleukin-5-producing CV-1 cells did not induce hyperresponsiveness. The percentage of eosinophils in broncho-alveolar lavage fluid was increased by 100% at 7 days but not at 3 days after administration of Interleukin-5-producing CV-1 cells. Antibody to Interleukin-5 prevented the broncho-alveolar lavage eosinophilia at 7 days after Interleukin-5 administration. It can be concluded that Interleukin-5- induces broncho-alveolar lavage eosinophilia and airway hyperresponsiveness and that these phenomena do not occur simultaneously. These data suggest a role for Interleukin-5 in the development of airway hyperresponsiveness in bronchial asthma.
Robert W. Egan - One of the best experts on this subject based on the ideXlab platform.
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Th2 cytokines and asthma — The role of Interleukin-5 in allergic eosinophilic disease
Respiratory research, 2001Co-Authors: Scott Greenfeder, Shelby P. Umland, Cuss Francis M, Richard W. Chapman, Robert W. EganAbstract:Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, Interleukin-5 is a very selective cytokine as a result of the restricted expression of the Interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of Interleukin-5 is a viable treatment. The present review addresses the data that relate Interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-Interleukin-5 monoclonal antibodies for the treatment of asthma in humans.
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th2 cytokines and asthma the role of Interleukin 5 in allergic eosinophilic disease
Respiratory Research, 2001Co-Authors: Scott Greenfeder, Shelby P. Umland, Richard W. Chapman, Francis M Cuss, Robert W. EganAbstract:Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, Interleukin-5 is a very selective cytokine as a result of the restricted expression of the Interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of Interleukin-5 is a viable treatment. The present review addresses the data that relate Interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-Interleukin-5 monoclonal antibodies for the treatment of asthma in humans.