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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3114-3122. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-02-0759. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0759v1 106/9/3114    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Qin, H. Articles by Benveniste, E. N. Search for Related Content PubMed PubMed Citation Articles by Qin, H. Articles by Benveniste, E. N. Related Collections Immunobiology Phagocytes Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY LPS induces CD40 gene expression through the activation of NF-B and STAT-1 in macrophages and microglia Hongwei Qin, Cynthia A. Wilson, Sun Jung Lee, Xueyan Zhao, and Etty N. Benveniste From the Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL. CD40 is expressed on various immune cells, including macrophages and microglia. Aberrant expression of CD40 is associated with autoimmune inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. Interaction of Toll-like receptor-4 (TLR4) with the Gram-negative bacteria endotoxin lipopolysaccharide (LPS) results in the induction of an array of immune response genes. In this study, we describe that LPS is a strong inducer of CD40 expression in macrophages and microglia, which occurs at the transcriptional level and involves the activation of the transcription factors nuclear factor-B (NF-B) and signal transducer and activator of transcription 1 (STAT-1). LPS-induced CD40 expression involves the endogenous production of the cytokine interferon-beta (IFN-), which contributes to CD40 expression by the activation of STAT-1. Blocking IFN-–induced activation of STAT-1 by IFN-–neutralizing antibody reduces LPS-induced CD40 gene expression. Furthermore, LPS induces acetylation and phosphorylation of histones H3 and H4 and the recruitment of NF-B, STAT-1, and RNA polymerase II on the CD40 promoter in vivo in a time-dependent manner, all events important for CD40 gene transcription. These results indicate that both LPS-induced NF-B activation and endogenous production of IFN- that subsequently induces STAT-1 activation play critical roles in the transcriptional activation of the CD40 gene by LPS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Beck, R. Penner, and A. Fleig Lipopolysaccharide-induced down-regulation of Ca2+ release-activated Ca2+ currents (ICRAC) but not Ca2+-activated TRPM4-like currents (ICAN) in cultured mouse microglial cells J. Physiol., January 15, 2008; 586(2): 427 - 439. [Abstract] [Full Text] [PDF] H. Qin, K. L. Roberts, S. A. Niyongere, Y. Cong, C. O. Elson, and E. N. Benveniste Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia J. Immunol., November 1, 2007; 179(9): 5966 - 5976. [Abstract] [Full Text] [PDF] S. Hong, A. Brass, M. Seman, F. Haag, F. Koch-Nolte, and G. R. 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Arbour, A. Bar-Or, and J. P. Antel Potential for interferon Beta-induced serum antibodies in multiple sclerosis to inhibit endogenous interferon-regulated chemokine/cytokine responses within the central nervous system. Arch Neurol, September 1, 2006; 63(9): 1296 - 1299. [Abstract] [Full Text] [PDF] O. Levy, E. E. Suter, R. L. Miller, and M. R. Wessels Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells Blood, August 15, 2006; 108(4): 1284 - 1290. [Abstract] [Full Text] [PDF] H. Qin, C. A. Wilson, S. J. Lee, and E. N. Benveniste IFN-{beta}-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia FASEB J, May 1, 2006; 20(7): 985 - 987. [Abstract] [Full Text] [PDF] C.-H. Chen, H. Floyd, N. E. Olson, D. Magaletti, C. Li, K. Draves, and E. A. Clark Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production Blood, February 15, 2006; 107(4): 1459 - 1467. 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