JAK2/STAT5 signaling pathway mediates Bojungbangdocktang enhanced hematopoiesis.
Bojungbangdocktang (BJBDT) is a medicinal herbal cocktail that has been used for cancer prevention and treatment in traditional Korean medicine. In the current study, BJBDT was demonstrated to regulate hematopoiesis. BJBDT significantly increased the expression of hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in hematopoietic stem cells (HSCs). Additionally, BJBDT enhanced the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) and STAT binding to gamma interferon activated sites (GAS) in HSCs. Furthermore, BJBDT significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Moreover, BJBDT increased the level of EPO at mRNA in kidney and plasma, and the numbers of erythroid-specific antigen Ter-119(+) erythroid cells in mice with aplastic anemia induced by 20% benzene. Consistently, histochemical staining revealed BJBDT increased the bone marrow and stromal cells as well as decreased macrophages and adipocytes in bone marrow tissues of mice with aplastic anemia. Taken together, the results suggest that BJBDT can enhance hematopoiesis via hematopoietic cytokine-mediated JAK2/STAT5 pathway as a potent hematopoietic candidate. Copyright © 2010 John Wiley & Sons, Ltd.
Lim
Jeonghan
J
College of Oriental Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
Jeong
Soo-Jin
SJ
Koh
Wonil
W
Han
Ihn
I
Lee
Hyo-Jung
HJ
Kwon
Tae-Rin
TR
Jung
Ji Hoon
JH
Kim
Jung Hyo
JH
Lee
Hyo-Jeong
HJ
Lee
Eun-Ok
EO
Kim
Sun-Hyung
SH
Lee
Min-Ho
MH
Kim
Sung-Hoon
SH
D000741:Anemia, Aplastic / Q000188:drug therapy; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008168:Lung / Q000166:cytology; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D050799:STAT5 Transcription Factor / Q000378:metabolism*
D016207:Cytokines; D010936:Plant Extracts; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2