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      Reciprocal Regulation of LTA 4 Hydrolase Expression in Human Monocytes by γ-Interferon and Interleukins 4 and 13: Potential Relevance to Leukotriene Regulation in Glomerular Disease

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          Abstract

          Background/Aims: Leukotriene A<sub>4</sub> (LTA<sub>4</sub>) hydrolase catalyzes the final step in the synthesis of leukotriene B<sub>4</sub> (LTB<sub>4</sub>). TH-1- and TH-2-derived cytokines may regulate LTB<sub>4</sub> synthesis by monocytes through their actions on the expression of LTA<sub>4</sub> hydrolase. Methods: Freshly isolated monocytes were incubated with pro- and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB<sub>4</sub> synthesis was determined by ELISA. Results: Interferon-γ (a TH-2-derived cytokine) increased significantly LTA<sub>4</sub> hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA<sub>4</sub> hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA<sub>4</sub> hydrolase after incubating the monocytes with either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1β did not show any significant effect on LTA<sub>4</sub> hydrolase mRNA expression. When LTB<sub>4</sub> release was measured, both IL-1β and interferon-γ significantly increased LTB<sub>4</sub> production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it. Conclusion: The opposing effects of TH-1- and TH-2-derived cytokines on the expression of LTA<sub>4</sub> hydrolase mRNA may regulate LTB<sub>4</sub> synthesis by monocytes during inflammation.

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            A unique signature identifies a family of zinc-dependent metallopeptidases.

            The primary sequence motif HExxH has been found in many zinc-dependent endopeptidases. We show that a larger signature comprising this sequence is common to most of the known zinc-dependent endopeptidases, and that the presence of the signature can be indicative of membership in the family. A search of the protein sequence databases for entries containing the signature retrieved several unexpected potential zinc endopeptidases.
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              Stimulation of human leukocyte degranulation by leukotriene B4and its ω-oxidized metabolites

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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2000
                October 2000
                31 July 2000
                : 8
                : 4-5
                : 258-265
                Affiliations
                Center for Glomerulonephritis, Renal Division, Emory University and Atlanta VA Medical Center, Atlanta, Ga., USA
                Article
                20677 Exp Nephrol 2000;8:258–265
                10.1159/000020677
                10940725
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, References: 48, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20677
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                γ-Interferon, Leukotrienes, Interleukins, Cytokines, LTA4 hydrolase

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