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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2004 Accepted August 5, 2004 Evidence that Genetic Deletion of the TNF Receptor p60 or p80 in Macrophages Modulates RANKL-Induced Signaling Yasunari Takada and Bharat B Aggarwal* Cytokine Research Laboratory, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA * Corresponding author; email: aggarwal{at}mdanderson.org. In the current report, we investigated the possibility of a cross-talk between RANKL and 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-/- < p80-/- < p60-/-p80-/-. The effect on NF-B activation correlated with RANKL-induced IB kinase activation. Deletion of both TNF receptors also potentiated RANKL-induced JNK, ERK1/2, and p38 MAPK activations in a dose- and time-dependent manner. NO production and expression of iNOS and COX-2 induced by RANKL was also maximally induced in double-knockout 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 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 two cytokines. 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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