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

J. Biol. Chem., Vol. 279, Issue 48, 49995-50003, November 26, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/48/49995    most recent M404246200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wessells, J. Articles by Johnson, P. F. Search for Related Content PubMed PubMed Citation Articles by Wessells, J. Articles by Johnson, P. F. Social Bookmarking                      What's this?

BCL-3 and NF-B p50 Attenuate Lipopolysaccharide-induced Inflammatory Responses in Macrophages^*

Jennifer Wessells, Mark Baer, Howard A. Young¶, Estefania Claudio||, Keith Brown||, Ulrich Siebenlist||, and Peter F. Johnson**

From the Laboratory of Protein Dynamics and Signaling and ^¶Laboratory of Experimental Immunology, NCI-Frederick, Frederick, Maryland 21702-1201 and ^||The Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892

Lipopolysaccharide (LPS) induces expression of tumor necrosis factor (TNF) and other pro-inflammatory cytokines in macrophages. Following its induction, TNF gene transcription is rapidly attenuated, in part due to the accumulation of NF-B p50 homodimers that bind to three B sites in the TNF promoter. Here we have investigated the inhibitory role of BCL-3, an IB-like protein that interacts exclusively with p50 and p52 homodimers. BCL-3 was induced by LPS with delayed kinetics and was associated with p50 in the nucleus. Forced expression of BCL-3 suppressed LPS-induced transcription from the TNF promoter and inhibited two artificial promoters composed of TNFB sites that preferentially bind p50 dimers. BCL-3-mediated repression was reversed by trichostatin A and was enhanced by overexpression of HDAC-1, indicating that transcriptional attenuation involves recruitment of histone deacetylase. Analysis of macrophages from p50 and BCL-3 knock-out mice revealed that both transcription factors negatively regulate TNF expression and that BCL-3 inhibits IL-1 and IL-1. In contrast, induction of the anti-inflammatory cytokine IL-10 was reduced in BCL-3 null macrophages. BCL-3 was not required for the production of p50 homodimers but BCL-3 expression was severely diminished in p50-deficient cells. Together, these findings indicate that p50 and BCL-3 function as anti-inflammatory regulators in macrophages by attenuating transcription of pro-inflammatory cytokines and activating IL-10 expression.

Received for publication, April 16, 2004 , and in revised form, September 24, 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.

Present address: KaloBios Pharmaceuticals, Inc., Palo Alto, CA 94304.

^** To whom correspondence should be addressed. Tel.: 301-846-1627; Fax: 301-846-5991; E-mail: johnsopf{at}ncifcrf.gov.

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

This article has been cited by other articles:

				M. Muhlbauer, P. M. Chilton, T. C. Mitchell, and C. Jobin Impaired Bcl3 Up-regulation Leads to Enhanced Lipopolysaccharide-induced Interleukin (IL)-23P19 Gene Expression in IL-10-/- Mice J. Biol. Chem., May 23, 2008; 283(21): 14182 - 14189. [Abstract] [Full Text] [PDF]

				R. E. Simmonds and B. M. Foxwell Signalling, inflammation and arthritis: NF-{kappa}B and its relevance to arthritis and inflammation Rheumatology, May 1, 2008; 47(5): 584 - 590. [Abstract] [Full Text] [PDF]

				J. Dagvadorj, Y. Naiki, G. Tumurkhuu, F. Hassan, S. Islam, N. Koide, I. Mori, T. Yoshida, and T. Yokochi Interleukin-10 inhibits tumor necrosis factor-{alpha} production in lipopolysaccharide-stimulated RAW 264.7 cells through reduced MyD88 expression Innate Immunity, April 1, 2008; 14(2): 109 - 115. [Abstract] [PDF]

				K. C. El Kasmi, A. M. Smith, L. Williams, G. Neale, A. Panopolous, S. S. Watowich, H. Hacker, B. M. J. Foxwell, and P. J. Murray Cutting Edge: A Transcriptional Repressor and Corepressor Induced by the STAT3-Regulated Anti-Inflammatory Signaling Pathway J. Immunol., December 1, 2007; 179(11): 7215 - 7219. [Abstract] [Full Text] [PDF]

				T. Hishiki, T. Ohshima, T. Ego, and K. Shimotohno BCL3 Acts as a Negative Regulator of Transcription from the Human T-cell Leukemia Virus Type 1 Long Terminal Repeat through Interactions with TORC3 J. Biol. Chem., September 28, 2007; 282(39): 28335 - 28343. [Abstract] [Full Text] [PDF]

				S.-D. Ha, D. Ng, J. Lamothe, M. A. Valvano, J. Han, and S. O. Kim Mitochondrial Proteins Bnip3 and Bnip3L Are Involved in Anthrax Lethal Toxin-induced Macrophage Cell Death J. Biol. Chem., September 7, 2007; 282(36): 26275 - 26283. [Abstract] [Full Text] [PDF]

				M. Touma, V. Antonini, M. Kumar, S. L. Osborn, A. M. Bobenchik, D. B. Keskin, J. E. Connolly, M. J. Grusby, E. L. Reinherz, and L. K. Clayton Functional Role for I{kappa}BNS in T Cell Cytokine Regulation As Revealed by Targeted Gene Disruption J. Immunol., August 1, 2007; 179(3): 1681 - 1692. [Abstract] [Full Text] [PDF]

				Y. de Kozak, B. Omri, J. R. Smith, M.-C. Naud, B. Thillaye-Goldenberg, and P. Crisanti Protein Kinase C{zeta} (PKC{zeta}) Regulates Ocular Inflammation and Apoptosis in Endotoxin-Induced Uveitis (EIU): Signaling Molecules Involved in EIU Resolution by PKC{zeta} Inhibitor and Interleukin-13 Am. J. Pathol., April 1, 2007; 170(4): 1241 - 1257. [Abstract] [Full Text] [PDF]

				M. F. Tomczak, S. E. Erdman, A. Davidson, Y. Y. Wang, P. R. Nambiar, A. B. Rogers, B. Rickman, D. Luchetti, J. G. Fox, and B. H. Horwitz Inhibition of Helicobacter hepaticus-Induced Colitis by IL-10 Requires the p50/p105 Subunit of NF-{kappa}B J. Immunol., November 15, 2006; 177(10): 7332 - 7339. [Abstract] [Full Text] [PDF]

				S. Cao, X. Zhang, J. P. Edwards, and D. M. Mosser NF-{kappa}B1 (p50) Homodimers Differentially Regulate Pro- and Anti-inflammatory Cytokines in Macrophages J. Biol. Chem., September 8, 2006; 281(36): 26041 - 26050. [Abstract] [Full Text] [PDF]

				P. M. Chilton and T. C. Mitchell CD8 T Cells Require Bcl-3 for Maximal Gamma Interferon Production upon Secondary Exposure to Antigen Infect. Immun., July 1, 2006; 74(7): 4180 - 4189. [Abstract] [Full Text] [PDF]

				H. T. Aung, K. Schroder, S. R. Himes, K. Brion, W. van Zuylen, A. Trieu, H. Suzuki, Y. Hayashizaki, D. A. Hume, M. J. Sweet, et al. LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression FASEB J, July 1, 2006; 20(9): 1315 - 1327. [Abstract] [Full Text] [PDF]

				C. M. Tato, N. Mason, D. Artis, S. Shapira, J. C. Caamano, J. H. Bream, H.-C. Liou, and C. A. Hunter Opposing roles of NF-{kappa}B family members in the regulation of NK cell proliferation and production of IFN-{gamma} Int. Immunol., April 1, 2006; 18(4): 505 - 513. [Abstract] [Full Text] [PDF]

				P. Qasimi, A. Ming-Lum, A. Ghanipour, C. J. Ong, M. E. Cox, J. Ihle, N. Cacalano, A. Yoshimura, and A. L-F. Mui Divergent Mechanisms Utilized by SOCS3 to Mediate Interleukin-10 Inhibition of Tumor Necrosis Factor {alpha} and Nitric Oxide Production by Macrophages J. Biol. Chem., March 10, 2006; 281(10): 6316 - 6324. [Abstract] [Full Text] [PDF]

				S. Ye Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome Cardiovasc Res, February 15, 2006; 69(3): 636 - 645. [Abstract] [Full Text] [PDF]

				M. F. Tomczak, M. Gadjeva, Y. Y. Wang, K. Brown, I. Maroulakou, P. N. Tsichlis, S. E. Erdman, J. G. Fox, and B. H. Horwitz Defective Activation of ERK in Macrophages Lacking the p50/p105 Subunit of NF-{kappa}B Is Responsible for Elevated Expression of IL-12 p40 Observed after Challenge with Helicobacter hepaticus J. Immunol., January 15, 2006; 176(2): 1244 - 1251. [Abstract] [Full Text] [PDF]

				D. Kashatus, P. Cogswell, and A. S. Baldwin Expression of the Bcl-3 proto-oncogene suppresses p53 activation Genes & Dev., January 15, 2006; 20(2): 225 - 235. [Abstract] [Full Text] [PDF]

				M. Jamaluddin, S. Choudhary, S. Wang, A. Casola, R. Huda, R. P. Garofalo, S. Ray, and A. R. Brasier Respiratory Syncytial Virus-Inducible BCL-3 Expression Antagonizes the STAT/IRF and NF-{kappa}B Signaling Pathways by Inducing Histone Deacetylase 1 Recruitment to the Interleukin-8 Promoter J. Virol., December 15, 2005; 79(24): 15302 - 15313. [Abstract] [Full Text] [PDF]

				S. Mathas, K. Johrens, S. Joos, A. Lietz, F. Hummel, M. Janz, F. Jundt, I. Anagnostopoulos, K. Bommert, P. Lichter, et al. Elevated NF-{kappa}B p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas Blood, December 15, 2005; 106(13): 4287 - 4293. [Abstract] [Full Text] [PDF]

				P. N. Moynagh The NF-{kappa}B pathway J. Cell Sci., October 15, 2005; 118(20): 4589 - 4592. [Full Text] [PDF]

				H. M. Wilson, S. Chettibi, C. Jobin, D. Walbaum, A. J. Rees, and D. C. Kluth Inhibition of Macrophage Nuclear Factor-{kappa}B Leads to a Dominant Anti-Inflammatory Phenotype that Attenuates Glomerular Inflammation in Vivo Am. J. Pathol., July 1, 2005; 167(1): 27 - 37. [Abstract] [Full Text] [PDF]