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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transl+Res
2015 ; 7
(10
): 1838-49
Nephropedia Template TP
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English Wikipedia
Matrine increases NKG2D ligand ULBP2 in K562 cells via inhibiting JAK/STAT3
pathway: a potential mechanism underlying the immunotherapy of matrine in
leukemia
#MMPMID26692928
Lu X
; Zhu Z
; Jiang L
; Sun X
; Jia Z
; Qian S
; Li J
; Ma L
Am J Transl Res
2015[]; 7
(10
): 1838-49
PMID26692928
show ga
PURPOSE: The study aimed to investigate the role of the JAK/STAT3 pathway in the
matrine induced ULBP2 expression on the human chronic myelogenous leukemia K562
cells. METHODS: K562 cells were cultured, and the relevant mRNA expressions were
detected. RESULTS: Matrine induced the expression of four NKG2D ligands on K562
cells, of which ULBP2 had the highest increase. After treatment with 0.8 mg/mL
matrine for 24 h, the mean fluorescence intensity (MFI) of ULBP2 increased. After
matrine treatment, the sensitivity of K562 cells to NK cell-mediated killing
increased significantly. After treatment with 0.2, 0.5 and 0.8 mg/ mL matrine,
the percentage of K562 cells killed by NK cells was significantly higher than
that of untreated cells (29.2%) (P<0.05). Matrine significantly inhibit the
protein expression of phosphorylated STAT 3 and JAK2. Matrine markedly inhibited
the IL-6 expression of K562 cells, and antagonized the IL-6 mediated STAT3 and
JAK2 phosphorylation. In addition, matrine enhanced the inhibitory effect of STAT
3 inhibitor on STAT 3 activity. The silencing of STAT expression and inhibition
of STAT3 activity significantly up-regulated the ULPB2 expression. Matrine had no
effect on the expression of IL-6R and gp130 on K562 cells, the mRNA expression of
IL-6R and gp130 increased slightly and the sgp 130 in cell supernatant
significantly increased. CONCLUSIONS: Our findings reveal IL-6 and IL-6
receptor-mediated JAK/STAT3 pathway is involved in the matrine induced
up-regulation of NKG2D ligands ULBP2 on K562 cells. Matrine might inhibit IL-6
expression and then suppress the activation of IL-6 receptor-mediated JAK/STAT3
pathway.