I-BET151 selectively regulates IL-6 production

Biochim Biophys Acta. 2014 Sep;1842(9):1549-55. doi: 10.1016/j.bbadis.2014.05.013. Epub 2014 May 22.


Orchestration of the inflammatory response is crucial for clearing pathogens. Although the production of multiple inflammatory cytokines has been thought to be regulated by common mechanisms, recent evidence indicates that the expression of some cytokines is differentially regulated by epigenetic regulatory mechanisms. In this study, we found that IL-6 production is selectively inhibited by the BET bromodomain protein (BRD) inhibitor I-BET151 in RAW264.7 cells stimulated with lipopolysaccharide (LPS), whereas I-BET151 did not alter the production of several other cytokines (TNFα, IL-1β and IL-10) at the concentration of IBET151 used. I-BET151 prevented the binding of CBP to the promoter of IL-6, but I-BET151 did not affect acetylation, phosphorylation, nuclear translocation, or DNA binding of p65-NF-κB. In vivo, I-BET151 treatment in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis decreased the early clinical symptoms, which are thought to be dependent on cytokine production. Altogether, these data suggest that targeting epigenetic-related proteins, such as BET proteins, may provide a strategy to reduce inflammation and the severity of inflammatory diseases, such as multiple sclerosis.

Keywords: Cytokines; I-BET151; Lipopolysaccharide; Macrophage; NF-κB.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Immunoprecipitation
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / pathogenicity*
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • NF-kappa B / metabolism
  • Peptide Fragments / toxicity
  • Phosphorylation / drug effects
  • Tuberculosis / complications
  • Tuberculosis / microbiology


  • Cytokines
  • GSK1210151A
  • Heterocyclic Compounds, 4 or More Rings
  • Interleukin-6
  • Lipopolysaccharides
  • Myelin-Oligodendrocyte Glycoprotein
  • NF-kappa B
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (34-56)