First Author | O'Driscoll CM | Year | 2015 |
Journal | J Neuroimmunol | Volume | 283 |
Pages | 23-9 | PubMed ID | 26004152 |
Mgi Jnum | J:321112 | Mgi Id | MGI:6882831 |
Doi | 10.1016/j.jneuroim.2015.04.005 | Citation | O'Driscoll CM, et al. (2015) Methyl CpG binding protein 2 deficiency enhances expression of inflammatory cytokines by sustaining NF-kappaB signaling in myeloid derived cells. J Neuroimmunol 283:23-9 |
abstractText | Knocking down methyl CpG binding protein 2 (MeCP2) enhances NF-kappaB 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 TNFalpha, 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. TNFalpha neutralizing antibody attenuated expression of IL-6 and TNFalpha but did not affect expression of IL-3. Lipopolysaccharide-mediated increases in TNFalpha, IL-6, and IL-3 mRNAs were also enhanced in MeCP2-deficient PBMC. Two inhibitors of NF-kappaB blocked the increased levels of IL-6, TNFalpha, and IL-3 in MeCP2-deficient PBMC treated with lipopolysaccharide. MeCP2 deficiency also enhanced expression of IL-6 and TNFalpha mRNAs in the THP1 human monocyte cell line, which were also attenuated by the NF-kappaB inhibitors. In chromatin immunoprecipitation assays, the binding of the NF-kappaB family member p65 and acetylated H3 to the TNFalpha promoter was greater after treatment with LPS in MeCP2-deficient THP1 cells. MeCP2 did not bind to the TNFalpha promoter. In summary, the data indicates that MeCP2 deficiency increases expression of TNFalpha and other inflammatory cytokines by enhancing NF-kappaB signaling. |