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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany
SGK1-MEDIATED NEGATIVE FEEDBACK REGULATION OF MATURATION AND IL-12 PRODUCTION IN DENDRITIC CELLS
Abstract number: P320
*Shumilina1 E., Xuan1 N.T., Lang1 F.
Dendritic cells (DCs) are antigen-presenting cells that provide a link between innate and adaptive immunity and are required for initiation of specific T cell-driven immune responses. Phosphoinositide 3 kinase (PI3K) activation suppresses proinflammatory cytokine production in DCs which limits excessive T helper (Th1) polarization. Little is known about the mechanisms of PI3K-mediated suppression in DCs. Downstream signaling elements of PI3K include the serum- and glucocorticoid-inducible kinase-1 (SGK1). The present study, therefore, explored whether DC functions are influenced by SGK1. To this end, DCs were isolated from the bone marrow of gene targeted mice lacking functional SGK1 (sgk1-/-) and their wild type littermates (sgk1+/+). Expression of maturation markers, MHC II, CD86 and CD54, analyzed by flow cytometry, and secretion of interleukin IL-12 upon lipopolysaccharide (LPS, 100 ng/ml) stimulation, determined by ELISA, were significantly higher in sgk1-/- than in sgk1+/+ DCs. According to FITC-dextran uptake, phagocytic capacity, which is lost upon DC maturation, was significantly lower in sgk1-/- than in sgk1+/+ DCs. Phosphorylation of inhibitory molecule IkB and the nuclear localization of the transcription factor NF-kB were significantly enhanced in sgk1-/- DCs as compared to sgk1+/+ DCs. Moreover, SGK1 suppressed p38 MAPK activity in DCs. Expression of CD86, MHCII and CD54, reflecting maturation status was significantly higher in DCs isolated from the spleen of sgk1-/- mice than those of sgk1+/+ mice. These observations point to an important role of SGK1 in the regulation of DC functions and thus disclose a novel element in the cross-talk between innate and adaptive immunity.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 201, Supplement 682 :P320