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.

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 δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

2018 ◽  
Vol 19 (10) ◽  
pp. 3022 ◽  
Author(s):  
Junjun Shen ◽  
Tao Yang ◽  
Youzhi Xu ◽  
Yi Luo ◽  
Xinyue Zhong ◽  
...  
Keyword(s):  
Rice Bran ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Activator Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

scholarly journals Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonietta Bernardo ◽  
Cristina Plumitallo ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Therapeutic Potential ◽  
Core Protein ◽  
Curcuma Longa ◽  
Demyelinating Diseases ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Conditions ◽  
Ppar Γ ◽  
Tnf Α ◽  
Anti Inflammatory

AbstractCurcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

scholarly journals RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome

2006 ◽  
Vol 154 (1) ◽  
pp. 159-166 ◽  
Author(s):  
M Messager ◽  
C Carrière ◽  
X Bertagna ◽  
Y de Keyzer
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Ectopic Acth Syndrome ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoid Tumours ◽  
Transcription Factor Genes

Objective: ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus. Design: Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome. Methods: Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms. Results: The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in <50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) γ2 were expressed in 50% of the tumours of each group whereas PPARγ1 was expressed in almost every tumour. Conclusions: ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation.

scholarly journals Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 222 ◽  
Author(s):  
Wenhui Jin ◽  
Longhe Yang ◽  
Zhiwei Yi ◽  
Hua Fang ◽  
Weizhu Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA–PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

15 Deoxy Δ12,14 PGJ2 Induces Procoagulant Activity in Cultured Human Endothelial Cells

2002 ◽  
Vol 87 (03) ◽  
pp. 523-529 ◽  
Author(s):  
Shaoping Xie ◽  
David O’Regan ◽  
Vijay Kakkar ◽  
Michael Scully
Keyword(s):  
Endothelial Cells ◽  
Peroxisome Proliferator ◽  
Endothelial Protein C Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Affinity Ligand ◽  
Ppar Γ ◽  
Tnf Α ◽  
Ea.Hy926 Cells ◽  
High Affinity Ligand ◽  
Feedback Regulator

Summary15 deoxy Δ12,14 PGJ2 (15d-PGJ2), a high affinity ligand of peroxisome proliferator-activated receptor γ (PPAR γ has been proposed to act as a negative feedback regulator of the inflammatory response. We investigated the effect of 15d-PGJ2 on the anticoagulant property of endothelial cells. 15d-PGJ2 stimulated a moderate but sustained increase in tissue factor (TF) activity in HUVECs and EA.hy926 cells while causing a partial loss of thrombomodulin (TM) activity. When cells were co-treated with 15d-PGJ2 and TNF-α, the subsequent elevation of TF activity was synergistically increased over that of cells treated with TNF-α, alone and the decline of TF activity after 24 h was less marked than TNF-α, alone. The induction of TF by 15d-PGJ2 alone and in combination with TNF-α, was reduced in the presence of PD 98059, suggesting the participation of the MEK/ERK pathway. The thiazolidinedione PPAR γ agonist ciglitazone had no effect on TF levels but reduced the expression of endothelial protein C receptor. The ability of 15d-PGJ2 to enhance a procoagulant phenotype arising from TNF-α, suggests a pro-inflammatory role for the prostaglandin.

scholarly journals Apple Flavonols Mitigate Adipocyte Inflammation and Promote Angiogenic Factors in LPS- and Cobalt Chloride-Stimulated Adipocytes, in Part by a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1386 ◽  
Author(s):  
Danyelle M. Liddle ◽  
Meaghan E. Kavanagh ◽  
Amanda J. Wright ◽  
Lindsay E. Robinson
Keyword(s):  
Mrna Expression ◽  
Cobalt Chloride ◽  
Nuclear Factor Κb ◽  
Diglycidyl Ether ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Anti Inflammatory

Adipose tissue (AT) expansion induces local hypoxia, a key contributor to the chronic low-grade inflammation that drives obesity-associated disease. Apple flavonols phloretin (PT) and phlorizin (PZ) are suggested anti-inflammatory molecules but their effectiveness in obese AT is inadequately understood. Using in vitro models designed to reproduce the obese AT microenvironment, 3T3-L1 adipocytes were cultured for 24 h with PT or PZ (100 μM) concurrent with the inflammatory stimulus lipopolysaccharide (LPS; 10 ng/mL) and/or the hypoxia mimetic cobalt chloride (CoCl2; 100 μM). Within each condition, PT was more potent than PZ and its effects were partially mediated by peroxisome proliferator-activated receptor (PPAR)-γ (p < 0.05), as tested using the PPAR-γ antagonist bisphenol A diglycidyl ether (BADGE). In LPS-, CoCl2-, or LPS + CoCl2-stimulated adipocytes, PT reduced mRNA expression and/or secreted protein levels of inflammatory and macrophage chemotactic adipokines, and increased that of anti-inflammatory and angiogenic adipokines, which was consistent with reduced mRNA expression of M1 polarization markers and increased M2 markers in RAW 264.7 macrophages cultured in media collected from LPS + CoCl2-simulated adipocytes (p < 0.05). Further, within LPS + CoCl2-stimulated adipocytes, PT reduced reactive oxygen species accumulation, nuclear factor-κB activation, and apoptotic protein expression (p < 0.05). Overall, apple flavonols attenuate critical aspects of the obese AT phenotype.

Sign in / Sign up

Export Citation Format

Share Document