NDRG2 is one of novel intrinsic factors for regulation of IL-10 production in human myeloid cell.
N-myc downstream-regulated gene 2 (NDRG2) implicated in cellular growth and differentiation was previously reported as it is specifically expressed in primary and in vitro-differentiated dendritic cells (DCs) from monocytes and CD34(+) progenitor cells. However, its function has yet to be investigated in DCs. Here, the novel NDRG2 function about modulation of cytokines in DC was observed in this study. The secretion of IL-10 was not found in the monocyte-derived DC cells with high level of NDRG2 expression, but IL-10 was abundantly secreted up to 1ng/ml in the monocyte-derived macrophages with low level of NDRG2 expression, and further confirmed that the expression of IL-10 was dramatically increased in NDRG2-silenced DCs under presence of LPS, and significantly reduced in the NDRG2-overexpressed U937 cells under stimulation of PMA. The secretion of IL-12p70 was significantly reduced in the siNDRG2 introduced DC cells. The intracellular signaling of IL-10 secretion was markedly inhibited by SB203580, inhibitor of p38 MAPK, in the LPS-activated DCs and phosphorylation of p38 MAPK was decreased in the NDRG2 introduced U937 cells under PMA-stimulation. Taken together, NDRG2 might have a pivotal role as one of intrinsic factors for the modulation of p38 MAPK phosphorylation, and subsequently involve in controlling of IL-10 production.
Choi
Seung-Chul
SC
Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
Kim
Kwang Dong
KD
Kim
Jong-Tae
JT
Oh
Sang-Seok
SS
Yoon
Sun Young
SY
Song
Eun Young
EY
Lee
Hee Gu
HG
Choe
Yong-Kyung
YK
Choi
Inpyo
I
Lim
Jong-Seok
JS
Kim
Jae Wha
JW
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D007093:Imidazoles; D008070:Lipopolysaccharides; C466228:NDRG2 protein, human; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580