Keeping up NF-κB appearances: Epigenetic control of immunity or inflammation-triggered epigenetics

Berghe, Wim Vanden; Ndlovu, Matladi N.; Hoya-Arias, Ruben; Dijsselbloem, Nathalie; Gerlo, Sarah; Haegeman, Guy

doi:10.1016/j.bcp.2006.07.012

Cited by 100 publications

(75 citation statements)

References 410 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 Suppression of NFkB attenuates microglial activation, thereby rendering the neuroprotection. 24,25 We found that, in the Jmjd3-knockdown N9 cells, the phosphorylation of NFkB was significantly enhanced, which might contribute to amplify the pro-inflammation (Figures 3e and f).…”

Section: Resultsmentioning

confidence: 99%

Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease

et al. 2013

View full text Add to dashboard Cite

Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either detrimental or beneficial effects in the central nervous system (CNS). Harnessing the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of Parkinson's disease (PD). However, the epigenetic mechanism that regulates microglia polarization remains elusive. Here, we reported that histone H3K27me3 demethylase Jumonji domain containing 3 (Jmjd3) was essential for M2 microglia polarization. Suppression of Jmjd3 in N9 microglia inhibited M2 polarization and simultaneously exaggerated M1 microglial inflammatory responses, which led to extensive neuron death in vitro. We also observed that the suppression of Jmjd3 in the substantia nigra (SN) in vivo dramatically caused microglial overactivation and exacerbated dopamine (DA) neuron death in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD. Moreover, we showed that the Jmjd3 level was lower in the midbrain of aged mice, which was accompanied by an elevated level of H3K27me3 and an increased ratio of M1 to M2 markers, suggesting that aging is an important factor in switching the microglia phenotypes. Overall, our studies indicate that Jmjd3 is able to enhance the polarization of M2 microglia by modifying histone H3K27me3, and therefore it has a pivotal role in the switch of microglia phenotypes that may contribute to the immune pathogenesis of PD.

show abstract

Section: Resultsmentioning

confidence: 99%

Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In truth, GCs probably utilize different mechanisms to inhibit NF-kB, depending on the 'environment', for example, the particular target gene (that is, not all NF-kB-driven gene promoters have the same TFbinding site composition to drive gene expression), the cell type-dependent presence of certain cofactors, the surrounding histone code (i.e., the particular set of chromatin modifications), etc. (Natoli and De Santa, 2006;Vanden Berghe et al, 2006b). Gene-repressing NRs should, therefore, be considered more as contextdependent, multitargeting effectors, rather than mediators of repression via a single pathway (De Bosscher et al, 2003a).…”

Section: Cross-talk Between Nrs and Nf-jbmentioning

confidence: 99%

“…Reciprocally, differential NF-kB target gene expression was recently found to rely on different (antagonistic) functions of the chromatinremodeling complexes Brg1, Brm, Mi-2b (nucleosome remodeling and histone deacetylase (NuRD)) (RamirezCarrozzi et al, 2006;Vanden Berghe et al, 2006b). Of special interest, expression of the Mi-2/NuRD complex component metastasis associated protein (MTA) is hormonally regulated and suggests that the stoechiometry of chromatin-remodeling complexes is under hormone control too (Fujita et al, 2003Bowen et al, 2004).…”

Section: Novel Prospects and Research Areasmentioning

confidence: 99%

“…Specifically, it is reported that certain maternal behaviors (increased pup licking and grooming and arched-back nursing) by rat mothers can alter the offspring's epigenome, including the DNA methylation status of the GR gene promoter in the hippocampus (Weaver et al, 2004;Meaney and Szyf, 2005;Szyf et al, 2005). However, further study is required to determine whether NF-kB transrepession by hormones is also susceptible to dynamic regulation by DNA methylation (Kirillov et al, 1996;Bird, 2003;Murayama et al, 2006;Vanden Berghe et al, 2006b). …”

Section: Novel Prospects and Research Areasmentioning

confidence: 99%

“…For example, much attention now focuses on learning how to read and interpret the 'histone code', inferring an additional level of dynamic gene regulation. Chromatin organization plays a major role in controlling the dynamic nature of NF-kB recruitment to target genes and represents an integration point for mediating diverse interactions between TFs (Burkhart et al, 2005;Natoli et al, 2005;Natoli and De Santa, 2006;Vanden Berghe et al, 2006b). This information is paramount for researchers interested in mechanisms of hormonal repression of NF-kB-driven gene expression, as additional key regulators of this process are still emerging.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cross-talk between nuclear receptors and nuclear factor κB

2006

View full text Add to dashboard Cite

A variety of studies have shown that some activated nuclear receptors (NRs), especially the glucorticoid receptor, the estrogen receptor and peroxisome proliferator-activated receptor, can inhibit the activity of the transcription factor nuclear factor jB (NF-jB), which plays a key role in the control of genes involved in inflammation, cell proliferation and apoptosis. This review describes the molecular mechanisms of cross-talk between NRs and NF-jB and the biological relevance of this crosstalk. The importance and mechanistic aspects of selective NR modulation are discussed. Also included are future research prospects, which will lead to a new era in the field of NR research with the aim of specifically inhibiting NF-jB-driven gene expression for anti-inflammatory, anti-tumor and immune-modulatory purposes.

show abstract