MyD88 Could Promote Multiple Myeloma Cells Growth and Survival

Abstract 5086

Toll like receptors (TLRs) are the major agents for innate immunity, which recognize invading microbial products. In previous study, we proved that activated TLR4 and TLR9 could promote MM cells growth and activated NF-κB signaling played a crucial role for ligands of TLR4 and TLR9 via increasing IL-6 autocrine. It was reported that MyD88 could play the key role in TLR signaling pathway and TLR4 and TLR9 shared the same MyD88-dependent pathway. In this study, we observed that expression of MyD88 mRNA in primary MM cells was higher than normal plasma cells and most of MM cell lines had a high MyD88 transcripts. Futher experiments demonstrated that transient over-expression of MyD88 could promote MM primary cells and MM cell lines growth and production of IL-6, IL-1, TNF-α, IFN-γ, VEGF and TGF-β. Moreover, down-regulation of MyD88 by sepecific virus based siRNA plamids in MM cell lines preliminarily resulted in reduced MM cells proliferation and increased MM cells apoptosis. These results highly suggested that MyD88 played a crucial role for TLR ligands to promote MM cells growth and survival, which make it possible to develop TLR system and MyD88 gene as the MM therapy target in the future.