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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 6, 2004 Accepted June 30, 2004 STAT3 regulates NF-B recruitment to the IL-12p40 promoter in dendritic cells Frank Hoentjen, Ryan B Sartor, Michitaka Ozaki, and Christian Jobin* Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Gastroenterology, Free University Medical Center, Amsterdam, The Netherlands Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan * Corresponding author; email: job{at}med.unc.edu. 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 NF-B and STAT3 in LPS-induced IL-12p40 gene expression in bone marrow derived dendritic cells (BMDC) isolated from wild-type (WT) and IL-10-/- mice. We report higher IL-12p40 mRNA accumulation and protein secretion in LPS-stimulated BMDC isolated from IL-10-/- compared to WT mice. LPS-induced NF-B signaling is similar in IL-10-/- and WT BMDC as measured by IB phosphorylation and degradation, RelA phosphorylation and nuclear translocation, and NF-B transcriptional activity, with no downregulatory effects of exogenous IL-10. Chromatin immunoprecipitation demonstrated enhanced cRel binding to the IL-12p40 promoter in IL-10-/- but not WT BMDC. Interestingly, LPS induced STAT3 phosphorylation in WT but not IL-10-/- BMDC, a process blocked by IL-10 receptor blocking antibody. Adenoviral gene delivery of a constitutively active STAT3 but not control 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: B Stoffels, J Schmidt, A Nakao, A Nazir, R S Chanthaphavong, and A J Bauer Role of interleukin 10 in murine postoperative ileus Gut, May 1, 2009; 58(5): 648 - 660. [Abstract] [Full Text] [PDF] K. L. W. Walton, L. Holt, and R. B. Sartor Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G601 - G611. [Abstract] [Full Text] [PDF] B. Hosten, C. Abbara, B. Petit, A. Dauvin, F. 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