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Blood, 15 January 2005, Vol. 105, No. 2, pp. 689-696. Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2004-04-1309. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1309v1 105/2/689    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 Hoentjen, F. Articles by Jobin, C. Search for Related Content PubMed PubMed Citation Articles by Hoentjen, F. Articles by Jobin, C. Related Collections Signal Transduction Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY STAT3 regulates NF-B recruitment to the IL-12p40 promoter in dendritic cells Frank Hoentjen, R. Balfour Sartor, Michitaka Ozaki, and Christian Jobin From the Center for Gastrointestinal Biology and Diseases, University of North Carolina at Chapel Hill, NC; Department of Gastroenterology, Free University Medical Center, Amsterdam, The Netherlands; Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan. Interleukin-10-deficient (IL-10-/-) mice develop an IL-12-mediated intestinal inflammation in the absence of endogenous IL-10. The molecular mechanisms of the dysregulated IL-12 responses in IL-10-/- mice are poorly understood. In this study, we investigated the role of nuclear factor- B (NF-B) and signal transducers and activators of transcription 3 (STAT3) in lipopolysaccharide (LPS)-induced IL-12p40 gene expression in bone marrow derived-dendritic cells (BMDCs) isolated from wild-type (WT) and IL-10-/- mice. We report higher IL-12p40 mRNA accumulation and protein secretion in LPS-stimulated BMDCs isolated from IL-10-/- compared with WT mice. LPS-induced NF-B signaling is similar in IL-10-/- and WT BMDCs as measured by IB phosphorylation and degradation, RelA phosphorylation and nuclear translocation, and NF-B transcriptional activity, with no down-regulatory effects of exogenous IL-10. Chromatin immunoprecipitation demonstrated enhanced NF-B (cRel, RelA) binding to the IL-12p40 promoter in IL-10-/- but not WT BMDCs. Interestingly, LPS induced STAT3 phosphorylation in WT but not IL-10-/- BMDCs, a process blocked by IL-10 receptor blocking antibody. Adenoviral gene delivery of a constitutively active STAT3 but not control green fluorescence protein (GFP) virus blocked LPS-induced IL-12p40 gene expression and cRel recruitment to the IL-12p40 promoter. In conclusion, dysregulated LPS-induced IL-12p40 gene expression in IL-10-/- mice is due to enhanced NF-B recruitment to the IL-12p40 promoter in the absence of activated STAT3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Muhlbauer, P. M. Chilton, T. C. Mitchell, and C. Jobin Impaired Bcl3 Up-regulation Leads to Enhanced Lipopolysaccharide-induced Interleukin (IL)-23P19 Gene Expression in IL-10-/- Mice J. Biol. Chem., May 23, 2008; 283(21): 14182 - 14189. [Abstract] [Full Text] [PDF] T. Karrasch, J.-S. Kim, M. Muhlbauer, S. T. Magness, and C. Jobin Gnotobiotic IL-10-/-;NF-{kappa}BEGFP Mice Reveal the Critical Role of TLR/NF-{kappa}B Signaling in Commensal Bacteria-Induced Colitis J. 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Gomez, J. Laborda, and M. J. M. Diaz-Guerra Notch-1 Up-Regulation and Signaling following Macrophage Activation Modulates Gene Expression Patterns Known to Affect Antigen-Presenting Capacity and Cytotoxic Activity J. Immunol., May 1, 2006; 176(9): 5362 - 5373. [Abstract] [Full Text] [PDF] M. F. Tomczak, M. Gadjeva, Y. Y. Wang, K. Brown, I. Maroulakou, P. N. Tsichlis, S. E. Erdman, J. G. Fox, and B. H. Horwitz Defective Activation of ERK in Macrophages Lacking the p50/p105 Subunit of NF-{kappa}B Is Responsible for Elevated Expression of IL-12 p40 Observed after Challenge with Helicobacter hepaticus J. Immunol., January 15, 2006; 176(2): 1244 - 1251. [Abstract] [Full Text] [PDF] N. Kamada, T. Hisamatsu, S. Okamoto, T. Sato, K. Matsuoka, K. Arai, T. Nakai, A. Hasegawa, N. Inoue, N. Watanabe, et al. Abnormally Differentiated Subsets of Intestinal Macrophage Play a Key Role in Th1-Dominant Chronic Colitis through Excess Production of IL-12 and IL-23 in Response to Bacteria J. 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