Tumor Necrosis Factor Alpha

The major effect of tumor necrosis factor alpha (TNF-a) is stimulation of IL-6 production in BMSCs. It upregu-lates the adhesion molecules on myeloma and BMSCs, and hence triggers IL-6 secretion from BMSCs via activation of NF-kB.88 89 TNF-a induces modest proliferation of myeloma cells via mitogen-activated protein kinase (MAPK)/ERK activation and not Stat3. It is possibly through the inhibition of the TNF-a pathway that proteosome inhibitors and thalidomide have their therapeutic effects. It also protects myeloma cells against drug-induced apoptosis.90

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