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NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production

  • Lee, Eun-Byul (Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University) ;
  • Kim, Ae-Yung (Department of Molecular Science and Technology, Ajou University) ;
  • Kang, Kyeong-Ah (Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University) ;
  • Kim, Hye-Ree (Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University) ;
  • Lim, Jong-Seok (Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University)
  • Received : 2010.11.09
  • Accepted : 2010.11.18
  • Published : 2010.12.31
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Abstract

Background: N-myc downstream regulated gene 2 (NDRG2) is a member of the NDRG gene family. Our previous report indicated a possible role for NDRG2 in regulating the cytokine, interleukin-10 (IL-10), which is an important immunosuppressive cytokine. Several pathways, including p38-MAPK, NF-${\kappa}B$, and JAK/STAT, are used for IL-10 production, and the JAK/STAT pathway can be inhibited in a negative feedback loop by the inducible protein, SOCS3. In the present study, we investigated the effect of NDRG2 gene expression on IL-10 signaling pathway that is modulated via SOCS3 and STAT3. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 in IL-10 production. U937 cells were also transfected with SOCS3- or NDRG2-specific siRNAs to examine whether the knockdown of SOCS3 or NDRG2 influenced IL-10 expression. Lastly, STAT3 and SOCS3 induction was measured to identify the signaling pathway that was associated with IL-10 production. Results: RT-PCR and ELISA assays showed that IL-10 was increased in U937-mock cells upon stimulation with PMA, but IL-10 was inhibited by overexpression NDRG2. After PMA treatment, STAT3 phosphorylation was decreased in a time-dependent manner in U937-mock cells, whereas it was maintained in U937-NDRG2 cells. SOCS3 was markedly reduced in U937-NDRG2 cells compared with U937-mock cells. IL-10 production after PMA stimulation was reduced in U937 cells when SOCS3 was inhibited, but this effect was less severe when NDRG2 was inhibited. Conclusion: NDRG2 expression modulates SOCS3 and STAT3 activity, eventually leading to the inhibition of IL-10 production.

Keywords

References

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