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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2005 Accepted June 30, 2005 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* Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA * Corresponding author; email: tika{at}uab.edu. 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 NF-B and 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.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: S. Fernandez-Lizarbe, M. Pascual, and C. Guerri Critical Role of TLR4 Response in the Activation of Microglia Induced by Ethanol J. Immunol., October 1, 2009; 183(7): 4733 - 4744. 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