Methyl CpG binding protein 2 deficiency enhances expression of inflammatory cytokines by sustaining NF-κB signaling in myeloid derived cells

Cliona M. O'Driscoll, Marina Palma Lima, Walter E. Kaufmann, Joseph P. Bressler

Research output: Research - peer-reviewArticle

Abstract

Knocking down methyl CpG binding protein 2 (MeCP2) enhances NF-κB activation in human peripheral blood mononuclear cells (PBMC). In this study, we examined whether this caused the expression of cytokines to be elevated. Increased levels of TNFα, IL-6, and IL-3 mRNAs were observed in human PBMC made MeCP2 deficient with a lentiviral shRNA MeCP2 vector and in splenocytes from MeCP2-null mice. TNFα neutralizing antibody attenuated expression of IL-6 and TNFα but did not affect expression of IL-3. Lipopolysaccharide-mediated increases in TNFα, IL-6, and IL-3 mRNAs were also enhanced in MeCP2-deficient PBMC. Two inhibitors of NF-κB blocked the increased levels of IL-6, TNFα, and IL-3 in MeCP2-deficient PBMC treated with lipopolysaccharide. MeCP2 deficiency also enhanced expression of IL-6 and TNFα mRNAs in the THP1 human monocyte cell line, which were also attenuated by the NF-κB inhibitors. In chromatin immunoprecipitation assays, the binding of the NF-κB family member p65 and acetylated H3 to the TNFα promoter was greater after treatment with LPS in MeCP2-deficient THP1 cells. MeCP2 did not bind to the TNFα promoter. In summary, the data indicates that MeCP2 deficiency increases expression of TNFα and other inflammatory cytokines by enhancing NF-κB signaling.

LanguageEnglish (US)
Pages23-29
Number of pages7
JournalJournal of Neuroimmunology
Volume283
DOIs
StatePublished - Jun 15 2015

Fingerprint

Methyl-CpG-Binding Protein 2
Protein Deficiency
Myeloid Cells
Cytokines
Interleukin-6
Interleukin-3
Blood Cells
Messenger RNA
Lipopolysaccharides
Chromatin Immunoprecipitation
Neutralizing Antibodies
Small Interfering RNA
Monocytes
Cell Line
Mouse Mecp2 protein

Keywords

  • Acetylated histone
  • MeCP2
  • NF-κB
  • P65
  • Peripheral blood mononuclear cells
  • TNFα

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology
  • Medicine(all)

Cite this

Methyl CpG binding protein 2 deficiency enhances expression of inflammatory cytokines by sustaining NF-κB signaling in myeloid derived cells. / O'Driscoll, Cliona M.; Lima, Marina Palma; Kaufmann, Walter E.; Bressler, Joseph P.

In: Journal of Neuroimmunology, Vol. 283, 15.06.2015, p. 23-29.

Research output: Research - peer-reviewArticle

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