scholarly journals Nuclear receptor peroxisome proliferator-activated receptor-gamma is activated in rat microglial cells by the anti-inflammatory drug HCT1026, a derivative of flurbiprofen

2005 ◽  
Vol 92 (4) ◽  
pp. 895-903 ◽  
Author(s):  
Antonietta Bernardo ◽  
Maria Antonietta Ajmone-Cat ◽  
Laura Gasparini ◽  
Ennio Ongini ◽  
Luisa Minghetti
Keyword(s):  
Nuclear Receptor ◽  
Microglial Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Drug ◽  
Anti Inflammatory

scholarly journals Inhibition of Cellular Proliferation through IκB Kinase-Independent and Peroxisome Proliferator-Activated Receptor γ-Dependent Repression of Cyclin D1

2001 ◽  
Vol 21 (9) ◽  
pp. 3057-3070 ◽  
Author(s):  
Chenguang Wang ◽  
Maofu Fu ◽  
Mark D'Amico ◽  
Chris Albanese ◽  
Jian-Nian Zhou ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Nuclear Receptor ◽  
Cellular Proliferation ◽  
Biological Effects ◽  
S Phase ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Iκb Kinase ◽  
Anti Inflammatory

ABSTRACT The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-regulated nuclear receptor superfamily member. Liganded PPARγ exerts diverse biological effects, promoting adipocyte differentiation, inhibiting tumor cellular proliferation, and regulating monocyte/macrophage and anti-inflammatory activities in vitro. In vivo studies with PPARγ ligands showed enhancement of tumor growth, raising the possibility that reduced immune function and tumor surveillance may outweigh the direct inhibitory effects of PPARγ ligands on cellular proliferation. Recent findings that PPARγ ligands convey PPARγ-independent activities through IκB kinase (IKK) raises important questions about the specific mechanisms through which PPARγ ligands inhibit cellular proliferation. We investigated the mechanisms regulating the antiproliferative effect of PPARγ. Herein PPARγ, liganded by either natural (15d-PGJ2 and PGD2) or synthetic ligands (BRL49653 and troglitazone), selectively inhibited expression of the cyclin D1 gene. The inhibition of S-phase entry and activity of the cyclin D1-dependent serine-threonine kinase (Cdk) by 15d-PGJ2 was not observed in PPARγ-deficient cells. Cyclin D1 overexpression reversed the S-phase inhibition by 15d-PGJ2. Cyclin D1 repression was independent of IKK, as prostaglandins (PGs) which bound PPARγ but lacked the IKK interactive cyclopentone ring carbonyl group repressed cyclin D1. Cyclin D1 repression by PPARγ involved competition for limiting abundance of p300, directed through a c-Fos binding site of the cyclin D1 promoter. 15d-PGJ2 enhanced recruitment of p300 to PPARγ but reduced binding to c-Fos. The identification of distinct pathways through which eicosanoids regulate anti-inflammatory and antiproliferative effects may improve the utility of COX2 inhibitors.

The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide

2004 ◽  
Vol 67 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Jesse Lo Verme ◽  
Jin Fu ◽  
Giuseppe Astarita ◽  
Giovanna La Rana ◽  
Roberto Russo ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anti Inflammatory

scholarly journals MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8425
Author(s):  
Giovanni Pallio ◽  
Angela D’Ascola ◽  
Luigi Cardia ◽  
Federica Mannino ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Monoamine Oxidase A ◽  
Microglial Cells ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Mao A ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1β (IL-1β). Control cells and IL-1β-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1β stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1β also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.

scholarly journals Probiotics, Nuclear Receptor Signaling, and Anti-Inflammatory Pathways

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Sonia S. Yoon ◽  
Jun Sun
Keyword(s):  
Nuclear Receptor ◽  
Human Microbiome ◽  
Peroxisome Proliferator ◽  
Receptor Signaling ◽  
Inflammatory Signaling ◽  
Peroxisome Proliferator Activated Receptor ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Clinical Conditions

There is increased investigation of the human microbiome as it relates to health and disease. Dysbiosis is implicated in various clinical conditions including inflammatory bowel disease (IBD). Probiotics have been explored as a potential treatment for IBD and other diseases. The mechanism of action for probiotics has yet to be fully elucidated. This paper discusses novel mechanisms of action for probiotics involving anti-inflammatory signaling pathways. We highlight recent progress in probiotics and nuclear receptor signaling, such as peroxisome-proliferator-activated receptor gamma (PPARγ) and vitamin D receptor (VDR). We also discuss future areas of investigation.

scholarly journals PPAR-γ Promotes the Polarization of Rat Retinal Microglia To M2 Phenotype By Regulating the Expression of CD200-CD200R1 Under Hypoxia

2022 ◽  
Author(s):  
Yiyi Hong ◽  
Li Jiang ◽  
Wei Huang ◽  
Wen Deng ◽  
Fen Tang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Peroxisome Proliferator Activated Receptor ◽  
Knock Down ◽  
Ppar Γ ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
M2 Phenotype

Abstract Objective Based on recent reports, peroxisome proliferator-activated receptor-γ (PPAR-γ) could promote microglial M2 polarization to inhibit inflammation. However, the specific molecular mechanisms instigate the anti-inflammatory ability of PPAR-γ in microglia have not been expounded. In the present study, we explored the molecular mechanisms of the anti-inflammatory effects of PPAR-γ in hypoxia-stimulated rat microglial cells. Methods shRNA expressing lentivirus was used to knock down PPAR-γ and CD200 genes. The hypoxia-induced polarization markers release (M1: iNOS, IL-1β, IL-6 and TNF-α; M2: Arg-1, YM1, IL-4 and IL-10) was assessed by RT-PCR, while PPAR-γ-related signals (PPAR-γ, PPAR-γ in cytoplasm or nucleus, CD200 and CD200Rs) were monitored by western blot and RT-PCR. Results Hypoxia enhanced PPAR-γ and CD200 expressions in microglial cells. In addition, PPAR-γ agonist 15d-PGJ2 elevated CD200 and CD200R1 expressions, while sh-PPAR-γ (PPAR-γ knock-down) had just the opposite effect. Following hypoxia, expressions of M1 markers increased significantly, while those of M2 markers decreased, and the above effects were attenuated by 15d-PGJ2. Conversely, knocking down PPAR-γ or CD200 inhibited the polarization of microglial cells to M2 phenotype. Conclusion Results demonstrated that PPAR-γ performed an anti-inflammatory function in hypoxia-stimulated microglial cells by promoting their polarization to M2 phenotype via CD200-CD200R1 pathway.

Radioprotective effect of pioglitazone against genotoxicity induced by ionizing radiation in human healthy lymphocytes

2020 ◽  
Vol 18 ◽  
Author(s):  
Roya Kazemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Anti Inflammatory ◽  
Sensitizing Effect ◽  
Binucleated Lymphocytes ◽  
Inflammatory Effect

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in human healthy lymphocytes. Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when were exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). Conclusion: The anti-inflammatory property is suggested the mechanism action of PG for protection human lymphocytes against genotoxicity induced by ionizing radiation.

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