Consistently, we demonstrated that HMCLs and fresh MM cells express IL-7 mRNA and secrete IL-7 in the presence of IL-6 and that bone marrow (BM) IL-7 levels were significantly higher in patients with MM.
Conversely, stimulation with IL-6 enhanced bFGF expression and secretion by myeloma cell lines (2-fold; P =.02) as well as MM patient cells (up to 3.6-fold; median, 1.5-fold; P =.002).
Cytogenetic studies were performed on BM cells after longterm cultures (6 days) with stimulation of cultures by granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF plus interleukin (IL)-6, IL-3 plus IL-6, or GM-CSF plus IL-3 plus IL-6 to improve myeloma cell growth, and 91 patients had an additional unstimulated culture.
DCZ3301 retained its activity against MM cells in the presence of exogenous cytokines (IL-6 or VEGF) or bone marrow stromal cells (BMSCs) and reduced activity of multiple signaling pathways (STAT3, NFκB, AKT, ERK1/2) in MM but not normal cells.
Deregulation of the expression of these interleukins was shown to be responsible for various diseases, such as i) IL-4 vs. immediate type hypersensitivity and ii) IL-6 vs. autoimmunity and multiple myelomas.
Down-regulation of interleukin 6 (IL6) by berberine might lead to inhibition of miR-21 transcription through STAT3 down-regulation in multiple myeloma.
EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts.
Electrophoretic mobility shift assays confirmed the involvement of NF-kappa B activation in regulating MM adhesion-induced IL-6 transcription in BMSCs.
Establishment and characterization of three myeloma cell lines that demonstrate variable cytokine responses and abilities to produce autocrine interleukin-6.
Establishment of a novel myeloma cell line KPMM2 carrying t(3;14)(q21;q32), which proliferates specifically in response to interleukin-6 through an autocrine mechanism.
Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and interferon- in interleukin-6 (IL-6)-dependent and IL-6-independent multiple myeloma cell lines.
Finally, combining CD126 and CD130 expression we found a significant increase of the percentage of CD126+ CD130+ patients at relapse, underlying the crucial role of IL-6 response in the late stage of MM.
For the first time, we show the actual contribution of downstream mediators, i.e., activated STAT factors, independent of the contribution of their upstream signaling pathways, on the proliferation and Dexamethasone rescue effects of IL-6 and IGF-1 in Multiple Myeloma.
Furthermore, combination therapy downregulated the NF-κB-targeted gene expression of interleukin 6 and manganese superoxide dismutase, which can induce chemo- and radio-resistance in MM.
Furthermore, two miRNAs, miR-19a and 19b, that are part of the miR-17 approximately 92 cluster, were shown to down regulate expression of SOCS-1, a gene frequently silenced in MM that plays a critical role as inhibitor of IL-6 growth signaling.
gamma-Interferon in multiple myeloma: inhibition of interleukin-6 (IL-6)-dependent myeloma cell growth and downregulation of IL-6-receptor expression in vitro.
Given the importance of IL-6 in multiple myeloma, the estrogen receptor-STAT3 or PPARgamma-STAT3 interaction may have significant therapeutic implications in multiple myeloma.