Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Biol. Chem. 284 (12): 7977-7985

© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Ribosomal Protein S19 Interacts with Macrophage Migration Inhibitory Factor and Attenuates Its Pro-inflammatory Function*

Ana-Maria Filip{ddagger}, Jörg Klug{ddagger}, Sevil Cayli{ddagger}, Suada Fröhlich{ddagger}, Tamara Henke{ddagger}, Philipp Lacher{ddagger}, Regina Eickhoff{ddagger}, Patrick Bulau§, Monika Linder, Christine Carlsson-Skwirut||, Lin Leng**, Richard Bucala**, Sandra Kraemer{ddagger}{ddagger}, Jürgen Bernhagen{ddagger}{ddagger}, , and Andreas Meinhardt{ddagger}1

{ddagger}Department of Anatomy and Cell Biology, Unit of Reproductive Biology, §Medical Clinic II, and Department of Biochemistry, Justus-Liebig-University of Giessen, Giessen D-35385, Germany, ||Department of Woman and Child Health, Paediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Karolinska Institute and University Hospital, S-1716 Stockholm, Sweden, **Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, and {ddagger}{ddagger}Department of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital of the RWTH Aachen, 52074 Aachen Germany

Abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in the pathogenesis of inflammatory disorders such as infection, sepsis, and autoimmune disease. MIF exists preformed in cytoplasmic pools and exhibits an intrinsic tautomerase and oxidoreductase activity. MIF levels are elevated in the serum of animals and patients with infection or different inflammatory disorders. To elucidate how MIF actions are controlled, we searched for endogenous MIF-interacting proteins with the potential to interfere with key MIF functions. Using in vivo biotin-tagging and endogenous co-immunoprecipitation, the ribosomal protein S19 (RPS19) was identified as a novel MIF binding partner. Surface plasmon resonance and pulldown experiments with wild type and mutant MIF revealed a direct physical interaction of the two proteins (KD = 1.3 x 10-6 M). As RPS19 is released in inflammatory lesions by apoptotic cells, we explored whether it affects MIF function and inhibits its binding to receptors CD74 and CXCR2. Low doses of RPS19 were found to strongly inhibit MIF-CD74 interaction. Furthermore, RPS19 significantly compromised CXCR2-dependent MIF-triggered adhesion of monocytes to endothelial cells under flow conditions. We, therefore, propose that RPS19 acts as an extracellular negative regulator of MIF.

Received for publication November 12, 2008. Revision received December 24, 2008.

* This work was supported by Deutsche Forschungsgemeinschaft Grants Me 1323/2-4 (to A. M.) and SFB 542/TP A7 (J. B.) and a research grant of the University Medical Centre Giessen and Marburg (to A. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Anatomy and Cell Biology, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen, Germany. Tel.: 49-641-9947024; Fax: 49-641-9947029; E-mail: andreas.meinhardt{at}anatomie.med.uni-giessen.de.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Active regulator of SIRT1 is required for ribosome biogenesis and function.
J. R. P. Knight, A. E. Willis, and J. Milner (2013)
Nucleic Acids Res. 41, 4185-4197
   Abstract »    Full Text »    PDF »
Macrophage Migration Inhibitory Factor Deficiency Is Associated With Impaired Killing of Gram-Negative Bacteria by Macrophages and Increased Susceptibility to Klebsiella pneumoniae Sepsis.
T. Roger, J. Delaloye, A.-L. Chanson, M. Giddey, D. Le Roy, and T. Calandra (2013)
The Journal of Infectious Disease 207, 331-339
   Abstract »    Full Text »    PDF »
Ribosomal Protein L17, RpL17, is an Inhibitor of Vascular Smooth Muscle Growth and Carotid Intima Formation.
E. M. Smolock, V. A. Korshunov, G. Glazko, X. Qiu, J. Gerloff, and B. C. Berk (2012)
Circulation 126, 2418-2427
   Abstract »    Full Text »    PDF »
A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease.
P. Renner, T. Roger, P.-Y. Bochud, T. Sprong, F. C. G. J. Sweep, M. Bochud, S. N. Faust, E. Haralambous, H. Betts, A.-L. Chanson, et al. (2012)
FASEB J 26, 907-916
   Abstract »    Full Text »    PDF »
Role of Subchondral Bone during Early-stage Experimental TMJ Osteoarthritis.
M. Embree, M. Ono, T. Kilts, D. Walker, J. Langguth, J. Mao, Y. Bi, J. L. Barth, and M. Young (2011)
Journal of Dental Research 90, 1331-1338
   Abstract »    PDF »
COP9 Signalosome Interacts ATP-dependently with p97/Valosin-containing Protein (VCP) and Controls the Ubiquitination Status of Proteins Bound to p97/VCP.
S. Cayli, J. Klug, J. Chapiro, S. Frohlich, G. Krasteva, L. Orel, and A. Meinhardt (2009)
J. Biol. Chem. 284, 34944-34953
   Abstract »    Full Text »    PDF »
Contributions of Zur-Controlled Ribosomal Proteins to Growth under Zinc Starvation Conditions.
S. E. Gabriel and J. D. Helmann (2009)
J. Bacteriol. 191, 6116-6122
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882