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

J. Biol. Chem., Vol. 277, Issue 27, 24243-24251, July 5, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/27/24243    most recent M200191200v1 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 Diakos, C. Articles by Zlabinger, G. J. Search for Related Content PubMed PubMed Citation Articles by Diakos, C. Articles by Zlabinger, G. J. Social Bookmarking                      What's this?

Novel Mode of Interference with Nuclear Factor of Activated T-cells Regulation in T-cells by the Bacterial Metabolite n-Butyrate^*

Christos Diakos, Eva E. Prieschl^§, Marcus Säemann, Veronica Novotny^§, Georg Böhmig^¶, Robert Csonga^§, Thomas Baumruker^§, and Gerhard J. Zlabinger

From the  Institute of Immunology, University of Vienna, Borschkegasse 8a, A-1090 Vienna, the ^§ Department of Allergic Diseases, Novartis Research Institute, Brunnerstrasse 53, A-1235 Vienna, and the ^¶ Department of Internal Medicine III, Division of Nephrology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

The transcription factor nuclear factor of activated T-cells (NF-AT) plays an essential role in the activation of many early immune response genes. A dynamic equilibrium between calcineurin and cellular kinases controls its phosphorylation and thus regulates its activity by determining its subcellular localization. Here, we demonstrate that T-cell activation in the presence of the bacterial metabolite n-butyrate, which leads to inhibition of interleukin-2 transcription, is characterized by the maintenance of the activity of counter-regulatory kinases glycogen synthase kinase 3 and protein kinase A as well as persistence of intracellular cAMP levels, whereas calcium response and mitogen-activated protein kinase activation were indistinguishable from cells stimulated in the absence of n-butyrate. Nuclear binding of NF-AT was decreased but other transcription factors implicated in interleukin-2 expression such as AP1 and nuclear factor B were unaffected. The effect on NF-AT binding appeared to be the result of increased nuclear export because the export inhibitor leptomycin B completely restored nuclear binding of NF-AT. We, therefore, provide first evidence for interference with NF-AT regulation alternative to the currently understood inhibition of nuclear import. This mechanism might represent a bacterial strategy to subvert host defense, which could be of particular clinical importance in the gastrointestinal tract where high amounts of n-butyrate are physiologically present.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. Bosisio, M. Vulcano, A. Del Prete, M. Sironi, V. Salvi, L. Salogni, E. Riboldi, F. Leoni, C. A. Dinarello, G. Girolomoni, et al. Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo J. Leukoc. Biol., December 1, 2008; 84(6): 1540 - 1548. [Abstract] [Full Text] [PDF]

				C. Nakamura, I. Matsushita, E. Kosaka, T. Kondo, and T. Kimura Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells Rheumatology, April 1, 2008; 47(4): 418 - 424. [Abstract] [Full Text] [PDF]

				T. Nakamura, T. Kukita, T. Shobuike, K. Nagata, Z. Wu, K. Ogawa, T. Hotokebuchi, O. Kohashi, and A. Kukita Inhibition of Histone Deacetylase Suppresses Osteoclastogenesis and Bone Destruction by Inducing IFN-{beta} Production J. Immunol., November 1, 2005; 175(9): 5809 - 5816. [Abstract] [Full Text] [PDF]