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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1100-1109. Prepublished online as a Blood First Edition Paper on April 27, 2004; DOI 10.1182/blood-2003-12-4302. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2003-12-4302v1 104/4/1100    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 BHATTACHARYYA, S. Articles by TISCH, R. Search for Related Content PubMed PubMed Citation Articles by BHATTACHARYYA, S. Articles by TISCH, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 19, 2003 Accepted April 5, 2004 Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and IB kinase activity SANDIP BHATTACHARYYA, PRADIP SEN, MARK WALLET, BRIAN LONG, ALBERT S BALDWIN, and ROLAND TISCH* Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA Lineberger Comprehensive Research Center, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Oral Biology, University of North Carolina, Chapel Hill, NC, USA Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Research Center, University of North Carolina, Chapel Hill, NC, USA; Curriculum in Oral Biology, University of North Carolina, Chapel Hill, NC, USA * Corresponding author; email: rmtisch{at}med.unc.edu. IL-10 has potent immunoregulatory effects on the maturation and antigen presenting cell (APC) function of dendritic cells (DC). The molecular basis underlying these effects in DC, however, is ill defined. It is well established that the transcription factor NF-B has a key role regulating DC development, maturation and APC function. This study was initiated to determine the effects of IL-10 on the NF-B signaling pathway in immature DC. IL-10 pretreatment of myeloid DC cultured from bone marrow resulted in reduced DNA binding and nuclear translocation of NF-B following anti-CD40 Ab or LPS stimulation. Furthermore, inhibition of NF-B activation was characterized by reduced: i) degradation and/or phosphorylation of IB and IB but not IB, and ii) phosphorylation of serine 536 located in the trans-activation domain of p65. Notably, IL-10 mediated inhibition of NF-B coincided with suppressed IB kinase (IKK) activity in vitro. Furthermore, inducible Akt phosphorylation was blocked by IL-10, and inhibitors of phosphatidylinositol 3-kinase (PI3K) effectively suppressed activation of Akt, IKK and NF-B. These findings demonstrate that IL-10 targets IKK activation in immature DC, and that blockade of the pathway is mediated in part through suppression of the PI3K pathway. 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] M. Minami, K. Shimizu, Y. Okamoto, E. Folco, M.-L. Ilasaca, M. W. Feinberg, M. Aikawa, and P. Libby Prostaglandin E Receptor Type 4-associated Protein Interacts Directly with NF-{kappa}B1 and Attenuates Macrophage Activation J. Biol. 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