SEARCH:   Advanced

Blood, 15 February 2008, Vol. 111, No. 4, pp. 1781-1788. Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-07-102343. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-07-102343v1 111/4/1781    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 Palmer, C. D Articles by Foxwell, B. M J Search for Related Content PubMed PubMed Citation Articles by Palmer, C. D Articles by Foxwell, B. M J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 23, 2007 Accepted October 21, 2007 Bmx tyrosine kinase regulates TLR4-induced IL-6 production in human macrophages independently of p38 MAPK and NFB activity Christine D Palmer, Brenda E Mutch, Sarita Workman, John P McDaid, Nicole J Horwood, and Brian M J Foxwell* Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, United Kingdom Royal Free Medical School, Dept of Immunology, University College London, London, United Kingdom * Corresponding author; email: b.foxwell{at}imperial.ac.uk. Chronic inflammation, as seen in conditions such as rheumatoid arthritis (RA) and Crohn's disease, is in part driven by discordant production of inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin (IL)-6. Tyrosine kinase activity is essential to LPS-induced cytokine production in monocytes, and previous studies by us and others have implicated a role for the Tec family kinase Bruton's tyrosine kinase (Btk) in inflammatory cytokine production. Here we show that knockdown of Btk using RNAi results in decreased TNF, but not IL-6 production. Further investigations into the signalling mechanisms regulating IL-6 production led to the discovery that the Tec kinase bone marrow tyrosine kinase gene in chromosome X (Bmx) regulates TLR-induced IL-6 production. Our data further showed that Bmx-dependent super-induction of IL-6 does not involve nuclear factor (NF)-B activity. More detailed investigations of pathways downstream of Bmx signalling revealed that Bmx targets the IL-6 3' untranslated region (UTR) to increase mRNA stabilisation via a novel, thus far undefined p38 mitogen activated protein kinase (MAPK)-independent pathway. These data have important implications for the design of therapeutics targeted against specific cytokines and their regulators in inflammatory disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Smith, F. Z. Rahman, B. Hayee, S. J. Graham, D. J.B. Marks, G. W. Sewell, C. D. Palmer, J. Wilde, B. M.J. Foxwell, I. S. Gloger, et al. Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease J. Exp. Med., August 31, 2009; 206(9): 1883 - 1897. [Abstract] [Full Text] [PDF] J. S. Lee, S. J. Shin, M. T. Collins, I. D. Jung, Y.-I. Jeong, C.-M. Lee, Y. K. Shin, D. Kim, and Y.-M. Park Mycobacterium avium subsp. paratuberculosis Fibronectin Attachment Protein Activates Dendritic Cells and Induces a Th1 Polarization Infect. Immun., July 1, 2009; 77(7): 2979 - 2988. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020