[Brain-derived neurotrophic factor promotes the secretion of MMP-9 in human myeloma cell through modulation of nucleus factor-kappaB].
OBJECTIVE
To explore the mechanism of brain-derived neurotrophic factor (BDNF) promoting human multiple myeloma (MM) cells secreting matrix metalloproteinase-9 ( MMP-9).


METHODS
Gelatin zymography of culture supernatants was performed to visualize the content of MMPs in myeloma RPMI 8226 cells stimulated by BDNF. NF-kappaB activity was determined by chemiluminescent electrophoretic mobility shift assay (EMSA).


RESULTS
Treatment with 25, 50, 100 and 200 microg/L BDNF for 24 h significantly (P < 0.01) enhanced the level of MMP-9 (2.03+/-0.48, 2.99+/-0.046, 4.63+/-0.62 and 5.62+/-1.29 microg/L, respectively, vs 1.00 microg/L of the control) secreted by RPMI8226 cells in a dose-dependent manner, while that of MMP-2 was not changed significantly (P > 0.05). The BDNF-induced activation of MMP-9 was inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, or K252 alpha, a specific tyrosine inhibitor of TrkB which is the receptor for BDNF. Pretreated with 1 mmol/L PDTC or 500 nmol/L K252 alpha significantly downregulated MMP-9 secreted by the 100 microg/L of BDNF stimulated RPMI 8226 cells (the optical density values were 867.52+/-101.81 and 727.98 +/-92.05, respectively, vs 1,159.01+/-233.15 of the control). The activity of NF-kappaB was enhanced by BDNF in a dose-dependent manner, and pretreatment with K252 alpha could significantly inhibit this activation at 1, 6, 12 and 24 h (P < 0.05) in a time-dependent manner.


CONCLUSIONS
BDNF plays an important role in the angiogenesis of MM to promote the up-regulation of MMP-9, which may be induced by enhanced NF-kappaB activity in MM cells.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Lu
L
Zhang
Yu
Y
Hu
Chun-Yan
CY
Sun
Jing
J
Huang
Zhang-Bo
ZB
Chu
D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D016328:NF-kappa B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9