Abstract
IL-6 signaling plays a crucial role in the pathogenesis of a number of diseases, including multiple myeloma, primary amyloidosis, cytokine release syndrome and other inflammatory conditions. It is central for the growth and survival of malignant plasma cells. IL-6R and IL-6ST receptors transduce IL-6 signaling. Molecular mechanisms regulating expression of IL-6R are not well understood and current therapies are based on monoclonal antibody to target IL-6 signaling. Small molecule inhibitors targeting IL-6 signaling are highly desirable. Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a. This is a novel finding and adds to existing therapies targeting IL-6 signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Biomarkers, Tumor / metabolism
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Bortezomib / pharmacology
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Cell Line, Tumor
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Dexamethasone / pharmacology
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Enzyme-Linked Immunosorbent Assay
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Humans
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Inhibitory Concentration 50
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Interleukin-6 / metabolism*
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Metformin / pharmacology*
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Multiple Myeloma / metabolism*
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Phenformin / pharmacology
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Plasma Cells / pathology
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Receptors, Interleukin-6 / metabolism*
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Sequence Analysis, RNA
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Signal Transduction
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Syndecan-1 / metabolism
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Thalidomide / analogs & derivatives
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Thalidomide / pharmacology
Substances
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Antibodies, Monoclonal
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Biomarkers, Tumor
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IL6R protein, human
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Interleukin-6
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Receptors, Interleukin-6
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SDC1 protein, human
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Syndecan-1
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Thalidomide
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Bortezomib
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Dexamethasone
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Metformin
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pomalidomide
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Phenformin