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Journal of Southern Medical University ; (12): 1809-1814, 2015.
Article in Chinese | WPRIM | ID: wpr-232521

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of glycogen synthase kinase 3β (GSK-3β) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs).</p><p><b>METHODS</b>Mature DCs (mDCs) induced by LPS were examined for GSK-3β phosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3β in maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3β, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR; the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3β and RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3β gene.</p><p><b>RESULTS</b>LPS exposure significantly lowered GSK-3β activity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3β inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3β obviously down-regulated the expression of RelB.</p><p><b>CONCLUSIONS</b>GSK-3β is a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3β is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3β, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3β overexpression supports GSK-3β as a new target for inducing tolerogenic DCs.</p>


Subject(s)
Animals , Mice , B7-2 Antigen , Metabolism , CD40 Antigens , Metabolism , Cell Differentiation , Cells, Cultured , Culture Media , Chemistry , Dendritic Cells , Glycogen Synthase Kinase 3 , Metabolism , Glycogen Synthase Kinase 3 beta , Indoles , Chemistry , Interleukin-10 , Metabolism , Interleukin-12 , Metabolism , Interleukin-6 , Metabolism , Lentivirus , Lymphocyte Culture Test, Mixed , Maleimides , Chemistry , Myeloid Cells , Phosphorylation , RNA, Messenger , Real-Time Polymerase Chain Reaction , Signal Transduction
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