scholarly journals Stimulatory Effects of Peroxisome Proliferator-Activated Receptor-γon FcγReceptor-Mediated Phagocytosis by Alveolar Macrophages

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
David M. Aronoff ◽  
Carlos H. Serezani ◽  
Jennifer K. Carstens ◽  
Teresa Marshall ◽  
Srinivasa R. Gangireddy ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Peroxisome Proliferator ◽  
Quiescent State ◽  
Peroxisome Proliferator Activated Receptor ◽  
Downstream Signaling ◽  
Surface Receptor ◽  
And Function

Alveolar macrophages abundantly express PPAR-γ, with both natural and synthetic agonists maintaining the cell in a quiescent state hyporesponsive to antigen stimulation. Conversely, agonists upregulate expression and function of the cell-surface receptor CD36, which mediates phagocytosis of lipids, apoptotic neutrophils, and other unopsonized materials. These effects led us to investigate the actions of PPAR-γagonists on the Fcγreceptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy-Δ12,14-prostaglandinJ2increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fcγreceptor. Receptor expression was not altered but activation of the downstream signaling proteins Syk, ERK-1, and ERK-2 was observed. Although it was previously known that PPAR-γligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.

scholarly journals Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically-ill COVID-19 patients

2020 ◽  
Author(s):  
Srikanth Mairpady Shambat ◽  
Alejandro Gómez-Mejia ◽  
Tiziano A. Schweizer ◽  
Markus Huemer ◽  
Chun-Chi Chang ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Distinct Pattern ◽  
Innate Immune ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Functional Responses ◽  
Innate Immune Signaling ◽  
Surface Receptor ◽  
And Function ◽  
Effector Response

AbstractCOVID-19 displays diverse disease severities and symptoms. Elevated inflammation mediated by hypercytokinemia induces a detrimental dysregulation of immune cells. However, there is limited understanding of how SARS-CoV-2 pathogenesis impedes innate immune signaling and function against secondary bacterial infections. We assessed the influence of COVID-19 hypercytokinemia on the functional responses of neutrophils and monocytes upon bacterial challenges from acute and corresponding recovery COVID-19 ICU patients. We show that severe hypercytokinemia in COVID-19 patients correlated with bacterial superinfections. Neutrophils and monocytes from acute COVID-19 patients showed severely impaired microbicidal capacity, reflected by abrogated ROS and MPO production as well as reduced NETs upon bacterial challenges. We observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes leading to a suppressive autocrine and paracrine signaling during bacterial challenges. Our data provide insights into the innate immune status of COVID-19 patients mediated by their hypercytokinemia and its transient effect on immune dysregulation upon subsequent bacterial infections

Deactivation of murine alveolar macrophages by peroxisome proliferator-activated receptor-γ ligands

2004 ◽  
Vol 286 (3) ◽  
pp. L613-L619 ◽  
Author(s):  
Raju C. Reddy ◽  
Venkateshwar G. Keshamouni ◽  
Shamsul H. Jaigirdar ◽  
Xianying Zeng ◽  
Todd Leff ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immune Effector ◽  
Ppar Γ ◽  
Oxidative Burst Activity ◽  
Mrna And Protein Expression ◽  
Oxide Synthase

Peroxisome proliferator-activated receptor-γ (PPAR-γ), a member of the nuclear hormone receptor family of ligand-dependent transcription factors, is a critical regulator of adipocyte differentiation and glucose metabolism. The expression, regulation, and functional significance of PPAR-γ in alveolar macrophages (AMs), the predominant resident immune effector cell within the alveolus, have not been previously examined. In this study, we show that, in contrast to peritoneal macrophages, resident murine AMs constitutively express high levels of PPAR-γ. Expression was primarily located in the nucleus by immunofluorescence staining. Quantitative real-time RT-PCR demonstrated that the predominant isoform was PPAR-γ2. Expression of PPAR-γ was induced by the anti-inflammatory cytokine IL-4. Treatment of murine AMs with PPAR-γ ligands suppresses PMA-stimulated oxidative burst activity and LPS + IFN-γ-mediated expression of inducible nitric oxide synthase. In addition, LPS-induced IL-12 mRNA and protein expression was inhibited by PPAR-γ ligands. These results support an important immunomodulatory role for PPAR-γ in AM responses.

scholarly journals A novel bioassay for quantification of surface Cannabinoid receptor 1 expression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ismael Rodríguez-Rodríguez ◽  
Joanna Kalafut ◽  
Arkadiusz Czerwonka ◽  
Adolfo Rivero-Müller
Keyword(s):  
Pain Perception ◽  
Cannabinoid Receptor ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Membrane Expression ◽  
Downstream Signaling ◽  
Physiological Processes ◽  
Surface Receptor ◽  
Receptor Surface Expression

Abstract The cannabinoid receptor type 1 (CB1) plays critical roles in multiple physiological processes such as pain perception, brain development and body temperature regulation. Mutations on this gene (CNR1), results in altered functionality and/or biosynthesis such as reduced membrane expression, changes in mRNA stability or changes in downstream signaling that act as triggers for diseases such as obesity, Parkinson’s, Huntington’s, among others; thus, it is considered as a potential pharmacological target. To date, multiple quantification methods have been employed to determine how these mutations affect receptor expression and localization; however, they present serious disadvantages that may arise quantifying errors. Here, we describe a sensitive bioassay to quantify receptor surface expression; in this bioassay the Gaussia Luciferase (GLuc) was fused to the extracellular portion of the CB1. The GLuc activity was assessed by coelenterazine addition to the medium followed by immediate readout. Based on GLuc activity assay, we show that the GLuc signals corelate with CB1 localization, besides, we showed the assay’s functionality and reliability by comparing its results with those generated by previously reported mutations on the CNR1 gene and by using flow cytometry to determine the cell surface receptor expression. Detection of membrane-bound CB1, and potentially other GPCRs, is able to quickly screen for receptor levels and help to understand the effect of clinically relevant mutations or polymorphisms.

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

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.

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

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