YC-1 enhances natural killer cell differentiation from hematopoietic stem cells.
NK cells play crucial roles in innate immunity and adaptive immunity. The detailed mechanisms, however, governing NK cell development remains unclear. In this study, we report that YC-1 significantly enhances NK cell populations differentiated from human umbilical cord blood hematopoietic stem cells (HSCs). NK cells increased by YC-1 display both phenotypic and functional features of fully mature NK (mNK) cells, but YC-1 does not affect the activation of mNK cells. YC-1 did not affect cGMP production and phosphorylation of STAT-5 which is essential for IL-15R signaling. On the other hand, YC-1 increased p38 MAPK phosphorylation during NK cell differentiation. Furthermore, p38 inhibitor SB203580 inhibited the differentiation of NK cells enhanced by YC-1. Taken together, these data suggest that YC-1 enhances NK cell differentiation through the activation of p38 MAPK which is involved in NK cell differentiation.
Yun
Sohyun
S
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
Lee
Suk Hyung
SH
Kang
Yun Hee
YH
Jeong
Mira
M
Kim
Mi Jeong
MJ
Kim
Mi Sun
MS
Piao
Zheng-Hao
ZH
Suh
Hyun-Woo
HW
Kim
Tae-don
TD
Myung
Pyung-Keun
PK
Yoon
Suk-Ran
SR
Choi
Inpyo
I
D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007191:Indazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D053647:Receptors, Interleukin-15 / Q000187:drug effects; D050799:STAT5 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007191:Indazoles; D011725:Pyridines; D053647:Receptors, Interleukin-15; D050799:STAT5 Transcription Factor; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D048051:p38 Mitogen-Activated Protein Kinases; D006152:Cyclic GMP; C093642:SB 203580