The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures
UNSPECIFIED (2004) The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures. BRITISH JOURNAL OF HAEMATOLOGY, 124 (3). pp. 366-375. ISSN 0007-1048Full text not available from this repository.
Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent assay were used to assess production of two key cytokines - vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) - and apoptosis in co-cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL-6 was almost exclusively produced by endothelial cells. In co-culture, there was significant up-regulation of VEGF and IL-6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co-cultures, with CC-10004 being more potent than CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co-cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co-culture partially protected myeloma cells from drug-induced apoptosis. This protective effect was probably due to IL-6 produced by endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody, but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RB Pathology|
|Journal or Publication Title:||BRITISH JOURNAL OF HAEMATOLOGY|
|Publisher:||BLACKWELL PUBLISHING LTD|
|Number of Pages:||10|
|Page Range:||pp. 366-375|
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