scholarly journals PPARγin Bacterial Infections: A Friend or Foe?

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Aravind T. Reddy ◽  
Sowmya P. Lakshmi ◽  
Raju C. Reddy
Keyword(s):  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Antibacterial Properties ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Therapeutic Modalities ◽  
Anti Inflammatory ◽  
And Function

Peroxisome proliferator-activated receptorγ(PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγactivation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγagonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPARγand its activation during bacterial infections, with focus on the potential of PPARγagonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPARγagonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system.

scholarly journals The Potential Applications of Peroxisome Proliferator-Activated ReceptorδLigands in Assisted Reproductive Technology

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Jaou-Chen Huang
Keyword(s):  
Assisted Reproductive Technology ◽  
Reproductive Function ◽  
Reproductive Technology ◽  
Embryonic Cell ◽  
Preimplantation Embryos ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Potential Applications ◽  
And Function

Peroxisome proliferator-activated receptorδ(PPARδ, also known as PPARβ) has ubiquitous distribution and extensive biological functions. The reproductive function of PPARδwas first revealed in the uterus at the implantation site. Since then, PPARδand its ligand have been discovered in all reproductive tissues, including the gametes and the preimplantation embryos. PPARδin preimplantation embryos is normally activated by oviduct-derived PPARδligand. PPARδactivation is associated with an increase in embryonic cell proliferation and a decrease in programmed cell death (apoptosis). On the other hand, the role of PPARδand its ligand in gamete formation and function is less well understood. This review will summarize the reproductive functions of PPARδand project its potential applications in assisted reproductive technology.

scholarly journals Bicyclic eremophilane-type petasite sesquiterpenes potentiate peroxisome proliferator–activated receptor γ activator–mediated inhibition of dendritic cells

2018 ◽  
Vol 32 ◽  
pp. 205873841878773
Author(s):  
Narcy Arizmendi ◽  
Chenjie Hou ◽  
Fujiang Guo ◽  
Yiming Li ◽  
Marianna Kulka
Keyword(s):  
Inflammatory Responses ◽  
Bone Marrow Cells ◽  
Surface Expression ◽  
Peroxisome Proliferator ◽  
Innate Immune Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonists ◽  
Anti Inflammatory ◽  
Secondary Lymphoid Organs ◽  
Dc Maturation

Dendritic cell (DC) activation induces expression of co-stimulatory surface molecules, as well as migration into secondary lymphoid organs, where they activate naïve T-cells. A family of plant derivatives, eremophilane-type petasite sesquiterpenes, can regulate the immune system through DC targeting due to their anti-inflammatory effects. Peroxisome proliferator–activated receptor gamma (PPARγ) is involved in inhibition of inflammatory responses and induction of DCs to acquire a mucosal phenotype. Since mucosal DCs are central in innate immune responses, we hypothesized that eremophilane-type petasite sesquiterpenes exerted their anti-inflammatory effects by inhibiting DC maturation and activation through PPARγ. This study assessed the bicyclic eremophilane-type petasite sesquiterpene compounds Fukinone and 10βH-8α,12-Epidioxyeremophil-7(11)-en-8β-ol (ZYFDC21 and ZYFDC22) in the maturation and activation of mouse DC. We measured surface expression of co-stimulatory molecules by flow cytometry and cell-free supernatant cytokine production upon lipopolysaccharide stimulation by enzyme-linked immunosorbent assays (ELISAs) in the presence or absence of PPARγ agonists. DCs were generated from C57BL/6 mice bone marrow cells and harvested. Cells were exposed to bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 in the presence or absence of synthetic PPARγ agonists (GW1929 and TGZ) or the natural PPARγ ligand 15d-PGJ2, followed by overnight activation with LPS. We observed differences in the upregulation of surface expression of CD86, along with TNF, IL-6, and IL-12p70 released by DCs stimulated with LPS, when using combinations of bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22, and PPARγ agonists, in particular the PPARγ ligand 15d-PGJ2. Our results indicate that bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 inhibit maturation and activation of DC, and this activity is augmented upon PPARγ activation.

Roles of histone deacetylation and AMP kinase in regulation of cardiomyocyte PGC-1α gene expression in hypoxia

2013 ◽  
Vol 304 (11) ◽  
pp. C1064-C1072 ◽  
Author(s):  
Angela Ramjiawan ◽  
Rushita A. Bagchi ◽  
Alexandra Blant ◽  
Laura Albak ◽  
Maria A. Cavasin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylation ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Glucose Depletion ◽  
And Function ◽  
Amp Activated Protein Kinase

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key determinant of cardiac metabolic function by regulating genes governing fatty acid oxidation and mitochondrial biogenesis. PGC-1α expression is reduced in many cardiac diseases, and gene deletion of PGC-1α results in impaired cardiomyocyte metabolism and function. Reduced fuel supply generally induces PGC-1α expression, but the specific role of oxygen deprivation is unclear, and the mechanisms governing PGC-1α gene expression in these situations are poorly understood. During hypoxia of primary rat cardiomyocytes up to 12 h, we found that PGC-1α expression was downregulated via a histone deacetylation-dependent mechanism. Conversely, extended hypoxia to 24 h concomitant with glucose depletion upregulated PGC-1α expression via an AMP-activated protein kinase (AMPK)-mediated mechanism. Our previous work demonstrated that estrogen-related receptor-α (ERRα) regulates PGC-1α expression, and we show here that overexpression of ERRα was sufficient to attenuate PGC-1α downregulation in hypoxia. We confirmed that chronic hypoxia downregulated cardiac PGC-1α expression in a hypoxic but nonischemic hypobaric rat model of pulmonary hypertension. Our data demonstrate that depletion of oxygen or fuel results in repression or induction, respectively, of PGC-1α expression via discrete mechanisms, which may contribute to cardiac energetic derangement during hypoxia, ischemia, and failure.

Peroxisome proliferator-activated receptor-γ inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells

2006 ◽  
Vol 291 (1) ◽  
pp. L84-L90 ◽  
Author(s):  
Sung Yong Lee ◽  
Eun Joo Kang ◽  
Gyu Young Hur ◽  
Ki Hwan Jung ◽  
Hye Cheol Jung ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Responses ◽  
Cigarette Smoke Exposure ◽  
Etiologic Factor ◽  
Peroxisome Proliferator ◽  
Cell Hyperplasia ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mucin Production ◽  
Ppar Γ ◽  
Anti Inflammatory

The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the ligand-activated nuclear receptor superfamily. PPAR-γ is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-γ agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-γ in smoke-induced mucin production. In this study, we investigated the effect of PPAR-γ agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-γ agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and downregulation of Akt expression. This study demonstrates that PPAR-γ agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium.

scholarly journals MicroRNA-511-3p mediated modulation of the peroxisome proliferator-activated receptor gamma (PPARγ) controls LPS-induced inflammatory responses in human monocyte derived DCs

2020 ◽  
Author(s):  
Dennis Awuah ◽  
Alisa Ruisinger ◽  
Meshal Alobaid ◽  
Chidimma Mbadugha ◽  
Amir M. Ghaemmaghami
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Monocyte ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Cytokine Production ◽  
And Function ◽  
First Time ◽  
Selection Of

AbstractThe peroxisome proliferator activated receptor gamma (PPARγ) is a ligand activated transcription factor expressed in dendritic cells (DCs), where it exerts anti-inflammatory responses against TLR4-induced inflammation. Recently, microRNA-511 (miR-511) has also emerged as a key player in controlling TLR4-mediated signalling, and in regulating the function of DCs. Interestingly, PPARγ has been previously highlighted as a putative target of miR-511 activity; however the link between miR-511 and PPARγ and its influence on human DC function within the context of LPS-induced inflammatory responses is unknown. Using a selection of miR-511-3p-specific inhibitors and mimics, we demonstrate for the first time that up or downregulation of miR-511-3p inversely correlates with PPARγ mRNA levels and transcriptional activity following treatment with PPARγ synthetic agonist rosiglitazone (RSG), in the presence or absence of LPS. Additionally, we show that PPARγ activation with RSG modulates LPS-induced DC activation and downregulates pro-inflammatory cytokine production following downregulation of miR-511-3p. Lastly, PPARγ activation was shown to suppress LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. These data suggest that PPARγ-induced modulation of DC phenotype and function is influenced by miR-511-3p expression, which may serve as a potential therapeutic target against inflammatory diseases.

scholarly journals The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes

2019 ◽  
Vol 316 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Simon T. Bond ◽  
Sarah C. Moody ◽  
Yingying Liu ◽  
Mete Civelek ◽  
Claudio J. Villanueva ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Mouse Strains ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Genes ◽  
And Function

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.

scholarly journals Peroxisome Proliferator Activated Receptor-αAgonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Justin L. Wilson ◽  
Rong Duan ◽  
Ahmed El-Marakby ◽  
Abdulmohsin Alhashim ◽  
Dexter L. Lee
Keyword(s):  
Angiotensin Ii ◽  
Inflammatory Markers ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Induced Hypertension ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Renal Expression

The anti-inflammatory properties of PPAR-αplays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-αagonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-αKO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-αKO mice compared to WT (161±4 mmHg versus145±4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134±7 mmHg). Plasma IL-6 levels were higher in PPAR-αKO mice on day 12 of Ang II infusion (30±4versus8±2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-αattenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.

scholarly journals Interferon-Stimulated Gene ISG12b1 Inhibits Adipogenic Differentiation and Mitochondrial Biogenesis in 3T3-L1 Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1217-1224 ◽  
Author(s):  
Bing Li ◽  
Jonghyun Shin ◽  
Kichoon Lee
Keyword(s):  
Mitochondrial Biogenesis ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Transcription ◽  
Peroxisome Proliferator Activated Receptor ◽  
And Function ◽  
Adipocyte Development

Microarray analysis was performed to find a new group of genes or pathways that might be important in adipocyte development and metabolism. Among them, a mouse interferon-stimulated gene 12b1 (ISG12b1) is expressed at a 400-fold higher level in adipocytes compared with stromal-vascular cells. It is predominantly expressed in adipose tissue among other tissues we tested. Developmentally, ISG12b1 mRNA expression was initially inhibited followed by a dramatic induction during both in vivo and in vitro adipogenic differentiation. Adenovirus-mediated overexpression of ISG12b1 inhibited adipogenic differentiation in 3T3-L1 cells as shown by decreased lipid staining with Oil-Red-O and reduction in adipogenic marker proteins including peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer-binding protein-α (C/EBPα). Our bioinformatics analysis for the predicted localization of ISG12b1 protein suggested the mitochondrial localization, which was confirmed by the colocalization of hemagglutinin-tagged ISG12b1 protein with mitochondrial marker MitoTracker. In addition, ISG12b1 protein was exclusively detected in protein extract from the fractionated mitochondria by Western blot analysis. Furthermore, overexpression of ISG12b1 in adipocytes reduced mitochondrial DNA content and gene expression of mitochondrial transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF1), and cytochrome oxidase II, suggesting an inhibitory role of ISG12b1 in mitochondrial biogenesis and function. Activation of mitochondrial biogenesis and function by treatment with PPARγ and PPARα agonists in 3T3-L1 cells and cold exposure in mice induced mitochondrial transcription factors and reduced ISG12 expression. These data demonstrated that mitochondrial-localized ISG12b1 protein inhibits adipocyte differentiation and mitochondrial biogenesis and function, implying the important role of mitochondrial function in adipocyte development and associated diseases. ISG12b1 is predominantly expressed in adipocytes and dramatically induced at the terminal stage of adipogenesis. Functionally, mitochondria-localized ISG12b1 inhibits adipogenic differentiation and mitochondria biogenesis.

scholarly journals Adipogenesis and lipotoxicity: role of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγcoactivator-1 (PGC1)

2007 ◽  
Vol 10 (10A) ◽  
pp. 1132-1137 ◽  
Author(s):  
Gema Medina-Gomez ◽  
Sarah Gray ◽  
Antonio Vidal-Puig
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Toxic Response ◽  
Increased Risk ◽  
And Function

AbstractObesity is characterised by an increase in the adipose deposits, resulting from an imbalance between food intake and energy expenditure. When expansion of the adipose tissue reaches its maximum limit, as in obesity, fat accumulates in non-adipose tissues such as liver, heart, muscle and pancreas, developing a toxic response known as lipotoxicity, a condition that promotes the development of insulin resistance and other metabolic complications. Thus, the lipotoxic state may contribute to the increased risk of insulin resistance, diabetes, fatty liver and cardiovascular complications associated with obesity.We are interested in studying adipose tissue, specifically how mechanisms of adipogenesis and remodelling of adipose tissue, in terms of size and function of the adipocytes, could be considered a strategy to increase the capacity for lipid storage and prevent lipotoxicity. The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors that regulate energy balance by promoting either energy deposition or energy dissipation. Under normal physiological conditions, PPARγ is mainly expressed in adipose tissue and regulates diverse functions such as the development of fat cells and their capacity to store lipids. The generation of PPARγ knockout mice, either tissue specific or isoform specific, has provided new models to study PPARγ’s role in adipose tissue differentiation and function and have highlighted the essential role of PPARγ in adipogenesis and lipogenesis.A second strategy to prevent lipotoxicity is to increase the capacity of tissues to oxidise fatty acids. PPARγcoactivator-1α is a coactivator of PPARγ that induces the expression of genes that promote the differentiation of preadipocytes to brown adipocytes. Recently, it has been implicated in increasing the oxidation of fatty acids via increasing mitochondrial capacity and function, making this co-factor a key candidate for the treatment of lipotoxicity.

scholarly journals Anticancer Role of PPARγAgonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-36 ◽  
Author(s):  
P. J. Simpson-Haidaris ◽  
S. J. Pollock ◽  
S. Ramon ◽  
N. Guo ◽  
C. F. Woeller ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Radiation Treatment ◽  
Inflammatory Responses ◽  
Combined Therapy ◽  
Chemotherapeutic Agents ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Peroxisome Proliferator Activated Receptor ◽  
Treatment And Prevention

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-γagonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγagonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγagonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγand/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

Sign in / Sign up

Export Citation Format

Share Document