[Effects of Yisui Jiedu Recipe on JAK2-STAT5 signal transduction pathway in bone marrow hematopoietic cells from patients with myelodysplastic syndrome-refractory anemia].
OBJECTIVE
To investigate the effect of Yisui Jiedu Recipe (YSJDR), a compound traditional Chinese herbal medicine, on cytokines and their corresponding just another kinase 2-signal transducers and activators of transcription 5 (JAK2-STAT5) signal transduction pathway in bone marrow hematopoietic cells from patients with myelodysplastic syndrome-refractory anemia (MDS-RA).


METHODS
Fluorogenic quantitative polymerase chain reaction (FQ-PCR) method was established to detect the levels of JAK2, STAT5 and Bcl-xL mRNA expressions, and JAK2-STAT5 signal transduction pathway was activated by granulocyte-macrophage-colony stimulating factor (GM-CSF) in cultured bone marrow hematopoietic cells from 10 patients with MDS-RA. The levels of interleukin-2 (IL-2), interleukin-3 (IL-3), gamma-interferon (gamma-INF) and tumor necrosis factor-alpha (TNF-alpha) in the cultural supernatant of untreated control, AG490-treated and YSJDF-treated cells were measured by enzyme-linked immunosorbent assay.


RESULTS
The levels of IL-2 and TNF-alpha in YSJDR-treated group were significantly lower than those in untreated control group and AG490-treated group (P<0.01, P<0.05), and IL-3 level in YSJDP-treated group was remarkably higher than that in the other two groups (P<0.01). There were no significant differences in the levels of IL-2 and IL-3 between AG490-treated group and untreated control group (P>0.05), while the TNF-alpha level in AG490-treated group was decreased obviously as compared with the untreated control group (P<0.01). There was no significant difference in gamma-INF level between YSJDR-treated group and AG490-treated group (P>0.05), while TNF-alpha level in the two groups were significantly lower than that in the untreated control group (P<0.01). The expressions of JAK2, STAT5 and Bcl-xL mRNAs were significantly down-regulated in the YSJDR-treated and the AG490-treated groups as compared with those in the untreated control group (P<0.05, P<0.01), while there were no differences in the expressions of JAK2, STAT5 and Bcl-xL mRNAs between YSJDR-treated group and AG490-treated group.


CONCLUSIONS
YSJDR can modulate cytokine level in bone marrow hematopoietic cells of MDS-RA, suppress JAK2-STAT5 signal transduction, and inhibit the Bcl-xL mRNA expression.
Tian
Sheng-Li
SL
Department of Hematology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. victorytian@126.com
Zhou
Yong-Ming
YM
Huang
Tao
T
Xue
Zhi-Zhong
ZZ
He
Wei
W
D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507924:JAK2 protein, human; D053614:Janus Kinase 2