HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 6, 4037-4047, February 11, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/6/4037    most recent M411569200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnson, B. J. Articles by Suhrbier, A. Search for Related Content PubMed PubMed Citation Articles by Johnson, B. J. Articles by Suhrbier, A. Social Bookmarking                      What's this?

Heat Shock Protein 10 Inhibits Lipopolysaccharide-induced Inflammatory Mediator Production^*

Barbara J. Johnson, Thuy T. T. Le¶, Caroline A. Dobbin, Tatjana Banovic¶, Christopher B. Howard, Flor de Maria Leon Flores, Daina Vanags, Dean J. Naylor, Geoffrey R. Hill¶, and Andreas Suhrbier¶

From the CBio Limited, 17 Wakefield St., Alderley, Queensland 4051, Australia and the ^¶Queensland Institute of Medical Research (Australian National Centre for International and Tropical Health and Nutrition and Department of Pathology, University of Queensland), 300 Herston Rd., Herston, Queensland 4029, Australia

Heat shock protein 10 (Hsp10) and heat shock protein 60 (Hsp60) were originally described as essential mitochondrial proteins involved in protein folding. However, both proteins have also been shown to have a number of extracellular immunomodulatory activities. Here we show that purified recombinant human Hsp10 incubated with cells in vitro reduced lipopolysaccharide (LPS)-induced nuclear factor-B activation and secretion of several inflammatory mediators from RAW264.7 cells, murine macrophages, and human peripheral blood mononuclear cells. Induction of tolerance by contaminating LPS was formally excluded as being responsible for Hsp10 activity. Treatment of mice with Hsp10 before endotoxin challenge resulted in the reduction of serum tumor necrosis factor- and RANTES (regulated upon activation, normal T cell expressed and secreted) levels and an elevation of serum interleukin-10 levels. Hsp10 treatment also delayed mortality in a murine graft-versus-host disease model, where gut-derived LPS contributes to pathology. We were unable to confirm previous reports that Hsp10 has tumor growth factor properties and suggest that Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60.

Received for publication, October 12, 2004

^* 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.

To whom correspondences should be addressed. Tel.: 61-7-3252-1022; Fax: 61-7-3252-1305; E-mail: barbara.johnson{at}cbio.com.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Broadley, D Vanags, B Williams, B Johnson, D Feeney, L Griffiths, S Shakib, G Brown, A Coulthard, P Mullins, et al. Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis Multiple Sclerosis, March 1, 2009; 15(3): 329 - 336. [Abstract] [PDF]

				B. Williams, D. Vanags, S. Hall, C. McCormack, P. Foley, J. Weiss, B. Johnson, E. Latz, and D. Feeney Efficacy and Safety of Chaperonin 10 in Patients With Moderate to Severe Plaque Psoriasis: Evidence of Utility Beyond a Single Indication Arch Dermatol, May 1, 2008; 144(5): 683 - 685. [Full Text] [PDF]

				G. A. Darnell, W. A. Schroder, J. Gardner, D. Harrich, H. Yu, R. L. Medcalf, D. Warrilow, T. M. Antalis, S. Sonza, and A. Suhrbier SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication J. Biol. Chem., October 20, 2006; 281(42): 31348 - 31358. [Abstract] [Full Text] [PDF]

				T. Ruby, C. Whittaker, D. R. Withers, M. K. Chelbi-Alix, V. Morin, A. Oudin, J. R. Young, and R. Zoorob Transcriptional profiling reveals a possible role for the timing of the inflammatory response in determining susceptibility to a viral infection. J. Virol., September 1, 2006; 80(18): 9207 - 9216. [Abstract] [Full Text] [PDF]

				B. Henderson, E. Allan, and A. R. M. Coates Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection Infect. Immun., July 1, 2006; 74(7): 3693 - 3706. [Full Text] [PDF]