März, Pia and Cheng, Jr-Gang and Gadient, Reto A. and Patterson, Paul H. and Stoyan, Tanja and Otten, Uwe and Rose-John, Stefan (1998) Sympathetic neurons can produce and respond to interleukin 6. Proceedings of the National Academy of Sciences of the United States of America, 95 (6). pp. 3251-3256. ISSN 0027-8424. PMCID PMC19728. http://resolver.caltech.edu/CaltechAUTHORS:MARpnas98
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Neuronal expression of cytokines is an area of active investigation in the contexts of development, disease, and normal neural function. Although cultured rat sympathetic neurons respond very weakly to exogenous interleukin 6 (IL-6), we find that addition of soluble IL-6 receptor (sIL-6R) and IL-6 enhances neuronal survival in the absence of nerve growth factor. Neutralizing monoclonal antibodies against IL-6 block these effects. Addition of IL-6 and sIL-6R also induces a subset of neuropeptide and transmitter synthetic enzyme mRNAs identical to that demonstrated for leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Both of these effects are duplicated by addition of a highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide chain, which is designated H-IL-6. In addition, we show that sympathetic neurons produce IL-6. In situ hybridization indicates a neuronal localization of IL-6 mRNA in superior cervical ganglia, and bioactive IL-6 protein is detected in ganglion culture supernatants. Interestingly, the IL-6 produced by sympathetic neurons does not lead to survival of these cells in culture unless sIL-6R is added. Thus, sympathetic neurons can produce IL-6 and may respond to it in an autocrine/paracrine manner if sIL-6R is present. Moreover, the prior findings of sIL-6R in serum and inflammatory fluids now have added interest in the context of neuroimmune interactions.
|Additional Information:||Copyright © 1998 by the National Academy of Sciences. Edited by Gerald D. Fischbach, Harvard Medical School, Boston, MA, and approved January 5, 1998 (received for review August 20, 1997). We thank Martina Fischer for the purification of rat recombinant sIL-6R. The skillful technical assistance of Beatrice Dimitriades-Schmutz and Doreen McDowell is also gratefully acknowledged. This work was supported by grants from the Deutsche Forschungsgemeinschaft (Bonn, Germany) and the Stiftung Innovation Rheinland-Pfalz (Mainz, Germany) to S.R.-J., from the Swiss National Foundation for Scientific Research and the Deutsche Forschungsgemeinschaft (SFB1523) to U.O., and from the National Institute of Neurological Disorders and Stroke (Bethesda) to P.H.P. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
|Subject Keywords:||CENTRAL-NERVOUS-SYSTEM; LEUKEMIA INHIBITORY FACTOR; IL-6R MESSENGER-RNAS; CILIARY NEUROTROPHIC FACTOR; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; GROWTH-FACTOR; POSTNATAL-DEVELOPMENT; CHOLINERGIC NEURONS; CRYSTAL-STRUCTURE|
|PubMed Central ID:||PMC19728|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||30 Jan 2006|
|Last Modified:||30 Dec 2015 07:22|
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