scholarly journals Parsing the Role of PPARs in Macrophage Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Toobian ◽  
Pradipta Ghosh ◽  
Gajanan D. Katkar
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Peroxisome Proliferator ◽  
Microbial Infection ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family

Cells are richly equipped with nuclear receptors, which act as ligand-regulated transcription factors. Peroxisome proliferator activated receptors (PPARs), members of the nuclear receptor family, have been extensively studied for their roles in development, differentiation, and homeostatic processes. In the recent past, there has been substantial interest in understanding and defining the functions of PPARs and their agonists in regulating innate and adaptive immune responses as well as their pharmacologic potential in combating acute and chronic inflammatory disease. In this review, we focus on emerging evidence of the potential roles of the PPAR subtypes in macrophage biology. We also discuss the roles of dual and pan PPAR agonists as modulators of immune cell function, microbial infection, and inflammatory diseases.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

A Mechanistic approach of Peroxisome Proliferator-Activated Receptors and its subtypes on Clinical and preclinical model of Neurodegenerative disorders

2021 ◽  
pp. 3967-3975
Author(s):  
Jinu Avarachan ◽  
Anitta Augustine ◽  
Pallavi Mahadev Shinde ◽  
Venkatesh Gunasekaran
Keyword(s):  
Neurodegenerative Disorders ◽  
Symptomatic Relief ◽  
Preclinical Model ◽  
Peroxisome Proliferator ◽  
Mechanistic Approach ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family ◽  
Preclinical And Clinical Studies ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, belonging to the nuclear receptor family, which has high expression of three structurally homologous PPARs isotypes (PPARα, PPARβ/δ, and PPARγ) in brain. Several studies have discovered role of PPARs in oxidative stress, mitochondrial dysfunction, neuroinflammation and production of the toxic proteins in various neurodegenerative disorders such as Parkinson disease, Alzheimer’s disease, Huntington disease, Amyotrophic Lateral Sclerosis, Multiple sclerosis etc. Currently available drugs provide symptomatic relief, but disease progression cannot be stopped, because of their unclear molecular approach. The ability of PPAR to modulate the pathways involved in these conditions paved a path for future studies. Due to increasing challenges to treat central nervous system related disorders, hence PPARs have attracted much attention nowadays. In this review, we discussed various mechanisms of PPARs subtypes in neurodegenerative disorders. We congregate the molecular evidences which support PPARs as a therapeutic target to treat neurodegenerative disorders from preclinical and clinical studies and provide a basis for the potential therapeutic use of PPAR ligands in human diseases.

Abstract 641: The Role of Interleukin-23 in the Development of Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Aliia Fatkhullina ◽  
Iuliia Peshkova ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Chronic Inflammatory Disease ◽  
Lymphoid Cells ◽  
Efficient Manner ◽  
Mediators Of Inflammation

Atherosclerosis is lipid-driven chronic inflammatory disease of the arterial wall mediated by innate and adaptive immune responses. Inflammation promotes the development atherosclerotic plaques. Cytokines are soluble mediators of inflammation and important players in the pathogenesis of atherosclerosis. IL-23, a cytokine of IL-6/IL-12 cytokines superfamily is produced by myeloid cells and regulates the production of IL-17 and IL-22 by T helper IL-17 producing (Th17) cells, innate lymphoid cells of type 3 (ILC3) and gamma delta T cells in various auto-inflammatory diseases. IL-23R expression was also detected on myeloid cells but its role in regulation of myeloid cell function is not well defined. The level of IL-23 was shown to be upregulated in cardiovascular pathologies. Therefore, we decided to address the role of IL-23 in atherosclerosis using Il23p19 and Il23(R) receptor deficient mice. Surprisingly, atherosclerosis prone, Ldlr -/- mice transplanted with Il23p19 -/- or Il23r -/- bone marrow and fed with Western diet (WD) for 14 weeks demonstrated acceleration of atherosclerosis progression, which was characterized by increased accumulation of various hematopoietic cells in the aortas. Analysis of cytokine production unexpectedly revealed no changes in IL-17A and IFN-gamma production among CD4 T cells in the aortas. This effect was specific to aortas, as IL-17A production in the intestine of Il23p19 -/- mice was reduced, similarly to previously published observations. On the other hand, macrophages from Il23p19 -/- mice were able to uptake oxLDL in more efficient manner compared to wt controls, suggesting the regulatory role of IL-23 in foam cells formation. We also found enhanced inflammatory gene expression in aortas of Il23p19 -/- -> Ldlr -/- and Il23r -/- -> Ldlr -/- mice compared to wt controls. Overall our data suggest IL-17 independent atheroprotective role of IL-23.

scholarly journals New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Miriam D. Neher ◽  
Sebastian Weckbach ◽  
Markus S. Huber-Lang ◽  
Philip F. Stahel
Keyword(s):  
Inflammatory Response ◽  
Major Trauma ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.

scholarly journals Enhanced Hepatocarcinogenicity Due to Agonists of Peroxisome Proliferator-Activated Receptors in Senescent Rats: Role of Peroxisome Proliferation, Cell Proliferation, and Apoptosis

2002 ◽  
Vol 2 ◽  
pp. 1491-1500 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Cell Proliferation ◽  
Peroxisome Proliferator ◽  
Carcinogenic Effect ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Findings ◽  
Proliferation And Apoptosis ◽  
Ppar Agonists ◽  
Old Rats ◽  
Peroxisome Proliferator Activated Receptors

Exposure to agonists of peroxisome proliferator-activated receptor alpha (PPARα) causes liver cancer in rodents, with aged animals being more susceptible than their younger counterparts to this effect. Treatment with these chemicals produced a five- to sevenfold higher yield of grossly visible hepatic tumors in old rats compared to young animals. The enhanced susceptibility of the aged livers to the carcinogenic effect of PPAR agonists could not be explained by differences in levels of peroxisomal and/or cell proliferation between young and old animals, as neither of these responses was exaggerated with aging. Reported studies have shown that activating PPARa results in the suppression of hepatic apoptosis. This effect is expected to diminish the ability of the liver to purge itself of pre-existing neoplastic cells, allowing them to progress to tumors. New findings from our laboratories show that the aged liver is exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition, aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2 than livers of young, adult, and middle-aged animals. Interestingly, the PPARa agonist Wy-14,643 significantly diminished elements of the proapoptotic machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably increasing elements of this machinery in younger animals. Taken together, while activation of PPARs appears to inhibit apoptosis in livers of senescent animals, activating these receptors seems to stimulate the apoptotic machinery in young animals. This paradoxical effect may be responsible for the exaggerated sensitivity of the aged liver to the carcinogenic effect of agents that activate PPARs.

scholarly journals Regulatory T cells in acute and chronic kidney diseases

2018 ◽  
Vol 314 (5) ◽  
pp. F679-F698 ◽  
Author(s):  
Rahul Sharma ◽  
Gilbert R. Kinsey
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Peripheral Tolerance ◽  
Autoimmune And Inflammatory Diseases

Foxp3-expressing CD4+ regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.

scholarly journals Therapeutic Targeting of Immune Cell Autophagy in Multiple Sclerosis: Russian Roulette or Silver Bullet?

2021 ◽  
Vol 12 ◽  
Author(s):  
Guan Yang ◽  
Luc Van Kaer
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Nerve Fibers ◽  
Therapeutic Approaches ◽  
Autoimmune Encephalomyelitis ◽  
Autoimmune And Inflammatory Diseases ◽  
The Central Nervous System

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which the immune system damages the protective insulation surrounding nerve fibers that project from neurons. The pathological hallmark of MS is multiple areas of myelin loss accompanied by inflammation within the CNS, resulting in loss of cognitive function that ultimately leads to paralysis. Recent studies in MS have focused on autophagy, a cellular self-eating process, as a potential target for MS treatment. Here, we review the contribution of immune cell autophagy to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS. A better understanding of the role of autophagy in different immune cells to EAE might inform the development of novel therapeutic approaches in MS and other autoimmune and inflammatory diseases.

scholarly journals Role of peroxisome proliferator-activated receptors in the control of alcohol dependence and concomitant liver pathology

2019 ◽  
Vol 16 (2) ◽  
pp. 244-256
Author(s):  
I. N. Semenenya ◽  
A. H. Shlyahtun ◽  
H. F. Raduta
Keyword(s):  
Liver Disease ◽  
Alcohol Dependence ◽  
Alcoholic Liver Disease ◽  
Therapeutic Potential ◽  
Scattered Data ◽  
Peroxisome Proliferator ◽  
Liver Pathology ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

The article is aimed to summarize the scattered data on the role of peroxisome proliferator-activated receptors (PPAR) and the possibility of using PPAR’s agonists for treatment of alcohol dependence and alcoholic liver disease. Earlier it was shown that some PPAR agonists can reduce ethanol consumption and preference in rodents. Several hypotheses considering the antialcoholic activity of PPAR agonists and the roles of PPAR in the development of alcohol dependence were discussed. In light of these data, the therapeutic potential of PPARs agonists as an agent for the treatment of alcoholism, has been reviewed.

scholarly journals Role of the Arylhydrocarbon Receptor (AhR) in the Pathology of Asthma and COPD

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takahito Chiba ◽  
Junichi Chihara ◽  
Masutaka Furue
Keyword(s):  
Inflammatory Diseases ◽  
Environmental Pollutants ◽  
Chronic Obstructive ◽  
Peroxisome Proliferator ◽  
Environmental Toxicants ◽  
Obstructive Pulmonary Disease ◽  
Mucin Production ◽  
Arylhydrocarbon Receptor ◽  
Peroxisome Proliferator Activated Receptors

The dioxins and dioxin-like compounds in cigarette smoke and environmental pollutants modulate immunological responses. These environmental toxicants are known to cause lung cancer but have also recently been implicated in allergic and inflammatory diseases such as bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). In a novel pathway of this response, the activation of a nuclear receptor, arylhydrocarbon receptor (AhR), mediates the effects of these toxins through the arachidonic acid cascade, cell differentiation, cell-cell adhesion interactions, cytokine expression, and mucin production that are implicated in the pathogenesis and exacerbation of asthma/COPD. We have previously reported that human bronchial epithelial cells express AhR, and AhR activation induces mucin production through reactive oxygen species. This review discusses the role of AhR in asthma and COPD, focusing in particular on inflammatory and resident cells in the lung. We describe the important impact that AhR activation may have on the inflammation phase in the pathology of asthma and COPD. In addition, crosstalk of AhR signaling with other ligand-activated transcription factors such as peroxisome proliferator-activated receptors (PPARs) has been well documented.

scholarly journals Treatment of Obesity-Related Complications with Novel Classes of Naturally Occurring PPAR Agonists

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Josep Bassaganya-Riera ◽  
Amir J. Guri ◽  
Raquel Hontecillas
Keyword(s):  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Peroxisome Proliferator ◽  
Punicic Acid ◽  
Ppar Γ ◽  
Naturally Occurring ◽  
Wide Range ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Treatment Of Obesity

The prevalence of obesity and its associated comorbidities has grown to epidemic proportions in the US and worldwide. Thus, developing safe and effective therapeutic approaches against these widespread and debilitating diseases is important and timely. Activation of peroxisome proliferator-activated receptors (PPARs) α, γ, and δ through several classes of pharmaceuticals can prevent or treat a variety of metabolic and inflammatory diseases, including type II diabetes (T2D). Thus, PPARs represent important molecular targets for developing novel and better treatments for a wide range of debilitating and widespread obesity-related diseases and disorders. However, available PPAR γ agonistic drugs such as Avandia have significant adverse side effects, including weight gain, fluid retention, hepatotoxicity, and congestive heart failure. An alternative to synthetic agonists of PPAR γ is the discovery and development of naturally occurring and safer nutraceuticals that may be dual or pan PPAR agonists. The purpose of this paper is to summarize the health effects of three plant-derived PPAR agonists: abscisic acid (ABA), punicic acid (PUA), and catalpic acid (CAA) in the prevention and treatment of chronic inflammatory and metabolic diseases and disorders.

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