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- Title
TNFα Mediated IL-6 Secretion Is Regulated by JAK/STAT Pathway but Not by MEK Phosphorylation and AKT Phosphorylation in U266 Multiple Myeloma Cells.
- Authors
Chansu Lee; Jeong-In Oh; Park, Juwon; Jee-Hye Choi; Eun-Kyung Bae; Hyun Jung Lee; Woo June Jung; Dong Soon Lee; Kwang-Sung Ahn; Sung-Soo Yoon
- Abstract
IL-6 and TNFα were significantly increased in the bone marrow aspirate samples of patients with active multiple myeloma (MM) compared to those of normal controls. Furthermore, MM patients with advanced aggressive disease had significantly higher levels of IL-6 and TNFα than those with MM in plateau phase. TNFα increased interleukin-6 (IL-6) production from MM cells. However, the detailed mechanisms involved in signaling pathways by which TNFα promotes IL-6 secretion from MM cells are largely unknown. In our study, we found that TNFα treatments induce MEK and AKT phosphorylation. TNFa-stimulated IL-6 production was abolished by inhibition of JAK2 and IKKß or by small interfering RNA (siRNA) targeting TNF receptors (TNFR) but not by MEK, p38, and PI3K inhibitors. Also, TNFa increased phosphorylation of STAT3 (ser727) including c-Myc and cyclin D1. Three different types of JAK inhibitors decreased the activation of the previously mentioned pathways. In conclusion, blockage of JAK/STATmediated NF-κB activation was highly effective in controlling the growth of MM cells and, consequently, an inhibitor of TNFα-mediated IL-6 secretion would be a potential new therapeutic agent for patients with multiple myeloma.
- Publication
BioMed Research International, 2013, Vol 2013, p1
- ISSN
2314-6133
- Publication type
Article
- DOI
10.1155/2013/580135