scholarly journals SETD1 and NF-κB Regulate Periodontal Inflammation through H3K4 Trimethylation

2020 ◽  
Vol 99 (13) ◽  
pp. 1486-1493 ◽  
Author(s):  
M. Francis ◽  
G. Gopinathan ◽  
A. Salapatas ◽  
S. Nares ◽  
M. Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Methylation ◽  
Gene Promoters ◽  
Cell Culture Model ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
H3k4 Trimethylation ◽  
Periodontal Inflammation ◽  
Culture Model

The inflammatory response to periodontal pathogens is dynamically controlled by the chromatin state on inflammatory gene promoters. In the present study, we have focused on the effect of the methyltransferase SETD1B on histone H3 lysine K4 (H3K4) histone trimethylation on inflammatory gene promoters. Experiments were based on 3 model systems: 1) an in vitro periodontal ligament (PDL) cell culture model for the study of SETD1 function as it relates to histone methylation and inflammatory gene expression using Porphyromonas gingivalis lipopolysaccharide (LPS) as a pathogen, 2) a subcutaneous implantation model to determine the relationship between SETD1 and nuclear factor κB (NF-κB) through its activation inhibitor BOT-64, and 3) a mouse periodontitis model to test whether the NF-κB activation inhibitor BOT-64 reverses the inflammatory tissue destruction associated with periodontal disease. In our PDL progenitor cell culture model, P. gingivalis LPS increased H3K4me3 histone methylation on IL-1β, IL-6, and MMP2 gene promoters, while SETD1B inhibition decreased H3K4me3 enrichment and inflammatory gene expression in LPS-treated PDL cells. LPS also increased SETD1 nuclear localization in a p65-dependent fashion and the nuclear translocation of p65 as mediated through SETD1, suggestive of a synergistic effect between SETD1 and p65 in the modulation of inflammation. Confirming the role of SETD1 in p65-mediated periodontal inflammation, BOT-64 reduced the number of SETD1-positive cells in inflamed periodontal tissues, restored periodontal tissue integrity, and enhanced osteogenesis in a periodontal inflammation model in vivo. Together, these results have established the histone lysine methyltransferase SETD1 as a key factor in the opening of the chromatin on inflammatory gene promoters through histone H3K4 trimethylation. Our studies also confirmed the role of BOT-64 as a potent molecular therapeutic for the restoration of periodontal health through the inhibition of NF-κB activity and the amelioration of SETD1-induced chromatin relaxation.

scholarly journals Effect of PGC-1αon Proliferation, Migration, and Transdifferentiation of Rat Vascular Smooth Muscle Cells Induced by High Glucose

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoqiang Qi ◽  
Yujing Zhang ◽  
Jing Li ◽  
Dongxia Hou ◽  
Yang Xiang
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

We assessed the role of PGC-1α (PPARγ coactivator-1 alpha) in glucose-induced proliferation, migration, and inflammatory gene expression of vascular smooth muscle cells (VSMCs). We carried out phagocytosis studies to assess the role of PGC-1α in transdifferentiation of VSMCs by flow cytometry. We found that high glucose stimulated proliferation, migration and inflammatory gene expression of VSMCs, but overexpression of PGC-1α attenuated the effects of glucose. In addition, overexpression of PGC-1α decreased mRNA and protein level of VSMCs-related genes, and induced macrophage-related gene expression, as well as phagocytosis of VSMCs. Therefore, PGC-1α inhibited glucose-induced proliferation, migration and inflammatory gene expression of VSMCs, which are key features in the pathology of atherosclerosis. More importantly, PGC-1α transdifferentiated VSMCs to a macrophage-like state. Such transdifferentiation possibly increased the portion of VSMCs-derived foam cells in the plaque and favored plaque stability.

scholarly journals Chemical epigenetics to assess the role of HDAC1–3 inhibition in macrophage pro-inflammatory gene expression

MedChemComm ◽  
2016 ◽  
Vol 7 (11) ◽  
pp. 2184-2190 ◽  
Author(s):  
Maria E. Ourailidou ◽  
Niek G. J. Leus ◽  
Kim Krist ◽  
Alessia Lenoci ◽  
Antonello Mai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Gene Expression ◽  
Murine Macrophages ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Azobenzene ortho-aminoanilides inhibit HDACs 1–3 and possess anti-inflammatory properties in murine macrophages.

scholarly journals Regulation of Macrophage Inflammatory Gene Expression by the Orphan Nuclear Receptor Nur77

2006 ◽  
Vol 20 (4) ◽  
pp. 786-794 ◽  
Author(s):  
Liming Pei ◽  
Antonio Castrillo ◽  
Peter Tontonoz
Keyword(s):  
Gene Expression ◽  
Nuclear Receptors ◽  
Transcriptional Activation ◽  
Liver X Receptor ◽  
Nuclear Hormone Receptor ◽  
Orphan Nuclear Receptor ◽  
Orphan Nuclear Receptors ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

Abstract Members of the nuclear hormone receptor superfamily have emerged as important regulators of macrophage gene expression in inflammation and disease. Previous studies have shown that the lipid-activated receptors peroxisomal proliferator-activated receptor and liver X receptor inhibit nuclear factor-κB (NF-κB) signaling and inflammatory gene expression. We recently identified the NR4A subfamily of orphan nuclear receptors (Nur77/NR4A1, Nurr1/NR4A2, and NOR1/NR4A3) as lipopolysaccharide- and NF-κB-responsive genes in macrophages. However, the role of these transcription factors in macrophage gene expression is unknown. We demonstrate here that, in contrast to peroxisomal proliferator-activated receptor and liver X receptor, the role of NR4A receptors in macrophages is proinflammatory. Retroviral expression of Nur77 in macrophages leads to the transcriptional activation of multiple genes involved in inflammation, apoptosis, and cell cycle control. One particularly interesting Nur77-responsive gene is the inducible kinase IKKi/IKKε, an important component of the NF-κB signaling pathway. The IKKi promoter contains a functional NR4A binding site and is activated by all three NR4A receptors in transient transfection assays. Consistent with the activation of IKKi, expression of Nur77 in macrophages potentiates the induction of inflammatory gene expression in response to lipopolysaccharide. These results identify a new role for NR4A orphan nuclear receptors in the control of macrophage gene expression during inflammation.

scholarly journals Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

2019 ◽  
Vol 40 (5) ◽  
pp. 1117-1131 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Tao Qin ◽  
Andreia Lopes de Morais ◽  
Kazutaka Sugimoto ◽  
Joon Yong Chung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Factor Α ◽  
The Relationship

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

scholarly journals Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: protective role of boron

2019 ◽  
Vol 8 (2) ◽  
pp. 262-269 ◽  
Author(s):  
Ulas Acaroz ◽  
Sinan Ince ◽  
Damla Arslan-Acaroz ◽  
Zeki Gurler ◽  
Hasan Huseyin Demirel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Bisphenol A ◽  
Protective Role ◽  
Albino Rats ◽  
Histopathological Changes ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Wistar Albino Rats

Boron reversed Bisphenol-A induced alterations.

Role of hormone-sensitive lipase in β-adrenergic remodeling of white adipose tissue

2007 ◽  
Vol 293 (5) ◽  
pp. E1188-E1197 ◽  
Author(s):  
Emilio P. Mottillo ◽  
Xiang Jun Shen ◽  
James G. Granneman
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Oxidative Capacity ◽  
Hormone Sensitive Lipase ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Hormone Sensitive

Free fatty acids (FFA) are important extracellular and intracellular signaling molecules and are thought to be involved in β-adrenergic-induced remodeling of adipose tissue, which involves a transient inflammatory response followed by mitochondrial biogenesis and increased oxidative capacity. This work examined the role of hormone-sensitive lipase (HSL), a key enzyme of acylglycerol metabolism, in white adipose tissue (WAT) remodeling using genetic inactivation or pharmacological inhibition. Acute treatment with the β3-adrenergic agonist CL-316,243 (CL) induced expression of inflammatory markers and caused extravasation of myeloid cells in WAT of wild-type (WT) mice. HSL-knockout (KO) mice had elevated inflammatory gene expression in the absence of stimulation, and acute injection of CL did not further recruit myeloid cells, nor did it further elevate inflammatory gene expression. Acute pharmacological inhibition of HSL with BAY 59-9435 (BAY) had no effect on inflammatory gene expression in WAT or in cultured 3T3-L1 adipocytes. However, BAY prevented induction of inflammatory cytokines by β-adrenergic stimulation in WAT in vivo and in cultured 3T3-L1 adipocytes. Chronic CL treatment stimulated mitochondrial biogenesis, expanded oxidative capacity, and increased lipid droplet fragmentation in WT mice, and these effects were significantly impaired in HSL-KO mice. In contrast to HSL-KO mice, mice with defective signaling of Toll-like receptor 4, a putative FFA receptor, showed normal β-adrenergic-induced remodeling of adipose tissue. Overall, results reveal the importance of HSL activity in WAT metabolic plasticity and inflammation.

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