Objective To investigate the expression of Toll-like receptor (TLR) in bone marrow mononuclear cells (BMMCs) of patients with multiple myeloma (MM) and its significance.Methods Totally 30 patients with MM were selected as observation group,and 10 patients with proliferative anemia were selected as control group.Patients in the observation group were treated with bortezomib combined with dexamethasone chemotherapy.The expression level of TLR in BMMCs was detected by real-time fluorescence quantitative method in both groups.The relationship between TLR and the clinical stages of MM was analyzed.Results The relative expression levels of TLR-4 and TLR-9 in BMMCs in the observation group were significantly higher than those in the control group (P ＜ 0.05).The expression levels of TLR-4 and TLR-9 in patients with different stages of MM showed significant differences (P ＜ 0.05).TLR-4 was positively correlated with M protein and β2-MG (r =0.673,0.466,P =0.023,0.041),and TLR-9 was also positively correlated with M protein and β2-MG (r =0.547,0.424,P =0.031,0.048).After treatment,the relative expression levels of TLR-4 and TLR-9 in BMMCs in patients with MM decreased significantly (P ＜ 0.05).Conclusion The expression levels of TLR-4 and TLR-9 are obviously higher in patients with MM,which is related to the clinical stage,M protein and β2-MG.

Objective To investigate the expression of Toll-like receptor (TLR) in bone marrow mononuclear cells (BMMCs) of patients with multiple myeloma (MM) and its significance.Methods Totally 30 patients with MM were selected as observation group,and 10 patients with proliferative anemia were selected as control group.Patients in the observation group were treated with bortezomib combined with dexamethasone chemotherapy.The expression level of TLR in BMMCs was detected by real-time fluorescence quantitative method in both groups.The relationship between TLR and the clinical stages of MM was analyzed.Results The relative expression levels of TLR-4 and TLR-9 in BMMCs in the observation group were significantly higher than those in the control group (P ＜ 0.05).The expression levels of TLR-4 and TLR-9 in patients with different stages of MM showed significant differences (P ＜ 0.05).TLR-4 was positively correlated with M protein and β2-MG (r =0.673,0.466,P =0.023,0.041),and TLR-9 was also positively correlated with M protein and β2-MG (r =0.547,0.424,P =0.031,0.048).After treatment,the relative expression levels of TLR-4 and TLR-9 in BMMCs in patients with MM decreased significantly (P ＜ 0.05).Conclusion The expression levels of TLR-4 and TLR-9 are obviously higher in patients with MM,which is related to the clinical stage,M protein and β2-MG.

PURPOSE: Tripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis. MATERIALS AND METHODS: TRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway. RESULTS: TRIM56 expression was prominently decreased in MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells. CONCLUSION: TRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.
Adaptor Proteins, Vesicular Transport/metabolism ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cytokines/secretion ; Disease Progression ; Down-Regulation/drug effects ; Gene Knockdown Techniques ; Humans ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Poly I-C/pharmacology ; Signal Transduction/drug effects ; Toll-Like Receptor 3/metabolism ; Tripartite Motif Proteins/deficiency ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/deficiency ; Ubiquitin-Protein Ligases/metabolism