Interleukin-6 (IL-6) is a key growth factor and thus plays a pivotal role in the pathogenesis of multiple myeloma. IL-6 is absolutely necessary for the cellular signalling cascade via JAK/STAT and RAS/MAPK pathways involved in proliferation and viability. We found interleukin (IL)-6 induced JAK-2 phosphorylation and induced proliferation of multiple myeloma cell line. Also phosphorylation of Stat1 and Stat3 was increased by IL-6 stimulation. Silencing JAK2 expression by small interfering RNA (siRNA) abrogated IL-6 induced phosphorylation of STAT3. In addition, soluble interleukin-6 receptor (sIL-6R) antagonized the function of hIL-6 and efficiently induced the growth arrest and apoptosis of U266 cells in a dose-dependent manner. Increasing levels of sIL-6R suppressed the phosphorylation of JAK-2 and Stat3. This suggests a comprehensive knowledge of the signaling and survival pathways could help find additional molecular targets and lead to the development of novel and more effective treatment strategies in multiple myeloma.

Topics:
interleukin-6, multiple myeloma, pmel17, signal transduction, squamous intraepithelial lesions, stat3 protein, rna, small interfering, growth factor, interleukins, mitogen-activated protein kinases

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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