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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4113-4121. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-04-1607. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1607v1 104/13/4113    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 Takada, Y. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Takada, Y. Articles by Aggarwal, B. B. Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling Yasunari Takada, and Bharat B. Aggarwal From the Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, TX. In the current report, we investigated the possibility of a cross-talk between receptor activator of NF-B ligand (RANKL) and tumor necrosis factor (TNF-) using macrophage cell lines derived from wild-type mice and from mice with genetic deletion of the type 1 TNF receptor (p60-/-), the type 2 TNF receptor (p80-/-), or both receptors (p60-/-p80-/-). Deletion of TNF receptors sensitized the cells to RANKL-induced NF-B activation, in order from least to most sensitive of p60-/- less than p80-/- less than p60-/-p80-/-. The effect on nuclear factor-B (NF-B) activation correlated with RANKL-induced IB kinase activation. Deletion of both TNF receptors also potentiated RANKL-induced c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK) activations in a dose- and time-dependent manner. Nitric oxide (NO) production and expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) induced by RANKL was also maximally induced in double knock-out cells. RANKL had no effect on the proliferation of wild-type cells, but deletion of TNF receptors induced growth modulatory effects. We also found that tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which mediates RANKL signaling, was constitutively bound to RANK in TNF receptor-deleted cells but not in wild-type cells, and this binding was enhanced by RANKL. Overall our results show that RANKL signaling is modulated by the TNF receptors and thus provide evidence of cross-talk between the receptors of 2 cytokines. (Blood. 2004;104: 4113-4121) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Zheng, X. Yu, P. Collin-Osdoby, and P. Osdoby RANKL Stimulates Inducible Nitric-oxide Synthase Expression and Nitric Oxide Production in Developing Osteoclasts: AN AUTOCRINE NEGATIVE FEEDBACK MECHANISM TRIGGERED BY RANKL-INDUCED INTERFERON-beta VIA NF-{kappa}B THAT RESTRAINS OSTEOCLASTOGENESIS AND BONE RESORPTION J. Biol. Chem., June 9, 2006; 281(23): 15809 - 15820. [Abstract] [Full Text] [PDF] S. K. Manna and G. T. Ramesh Interleukin-8 Induces Nuclear Transcription Factor-{kappa}B through a TRAF6-dependent Pathway J. Biol. Chem., February 25, 2005; 280(8): 7010 - 7021. [Abstract] [Full Text] [PDF]

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