CVI Accepts, published online ahead of print on 19 November 2008

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, X. Articles by McCall, C. E. Search for Related Content PubMed PubMed Citation Articles by Chen, X. Articles by McCall, C. E.

 Previous Article  |  Next Article 

Clin. Vaccine Immunol. doi:10.1128/CVI.00320-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

RelB sustains IB expression during endotoxin tolerance

Xiaoping Chen^*, Barbara K. Yoza, Mohamed El Gazzar, Jean Y.Q. Hu, Sue L. Cousart, and Charles E. McCall

Department of Internal Medicine, Section of Molecular Medicine, and Department of General Surgery, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA

^* To whom correspondence should be addressed. Email: xchen{at}wfubmc.edu.

Transcription factors and chromatin structural modifiers induce clinically relevant epigenetic modifications of blood leukocytes during severe systemic inflammation (SSI) in humans and animals. These changes affect genes with distinct functions, as exemplified by silencing of a set of acute proinflammatory genes and sustained expression of a group of anti-microbial and anti-inflammatory genes. This paradigm is closely mimicked in the THP-1 human pro-monocyte cell model of lipopolysaccharide (LPS) endotoxin tolerance. We previously reported that LPS induced de novo expression of RelB is required for generating tolerance to IL-1 and TNF expression. RelB represses transcription by binding with heterochromatic protein 1 (HP-1) to the proximal promoters of IL-1 and TNF. In contrast, we report herein that RelB is required for sustained expression of anti-inflammatory IB in LPS tolerant THP-1 cells. RelB transcription activation requires binding to the IB proximal promoter along with NF-B p50, and is associated with an apparent dimer exchange with p65. We also observe that RelB induced during human SSI binds to the IB proximal promoter of circulating leukocytes. We conclude that RelB functions as a dual transcription regulator during LPS tolerance and human SSI by activating and repressing innate immunity genes.

This article has been cited by other articles:

• Chen, X., El Gazzar, M., Yoza, B. K., McCall, C. E. (2009). The NF-{kappa}B Factor RelB and Histone H3 Lysine Methyltransferase G9a Directly Interact to Generate Epigenetic Silencing in Endotoxin Tolerance. J. Biol. Chem. 284: 27857-27865 [Abstract] [Full Text]