ArticleThe Journal of biological chemistry2011
Peroxisome proliferator-activated receptor gamma negatively regulates IFN-beta production in Toll-like receptor (TLR) 3- and TLR4-stimulated macrophages by preventing interferon regulatory factor 3 binding to the IFN-beta promoter.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns (Review).International journal of molecular medicine · 2016Pooled it
- Network analysis identifies a putative role for the PPAR and type 1 interferon pathways in glucocorticoid actions in asthmatics.BMC medical genomics · 2012Trial
- Effect of eicosapentaenoic acid on innate immune responses in Atlantic salmon cells infected with infectious salmon anemia virus.Virology journal · 2025Article
- Effects of eicosapentaneoic acid on innate immune responses in an Atlantic salmon kidney cell line in vitro.PloS one · 2024Article
- Endocannabinoid 2-Arachidonoylglycerol Synthesis and Metabolism at Neuronal Nuclear Matrix Fractions Derived from Adult Rat Brain Cortex.International journal of molecular sciences · 2023Article
- PPARs and the Kynurenine Pathway in Melanoma-Potential Biological Interactions.International journal of molecular sciences · 2023Review
- Amplified Gliosis and Interferon-Associated Inflammation in the Aging Brain following Diffuse Traumatic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Protection against influenza-induced Acute Lung Injury (ALI) by enhanced induction of M2a macrophages: possible role of PPARγ/RXR ligands in IL-4-induced M2a macrophage differentiation.Frontiers in immunology · 2022Article
- Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3.Cell death and differentiation · 2021Article
- A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection.Nature genetics · 2021Article
- The effect of fenofibrate, a PPARα activator on toll-like receptor-4 signal transduction in melanoma both in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Article
- Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure.Frontiers in genetics · 2020Article
- Article
- Crosstalk between Peroxisome Proliferator-Activated Receptors and Toll-Like Receptors: A Systematic Review.Advanced pharmaceutical bulletin · 2019Review
- Interferon Regulatory Factor 3 Deficiency Induces Age-Related Alterations of the Retina in Young and Old Mice.Frontiers in cellular neuroscience · 2019Article
- PPARγ Deficiency Suppresses the Release of IL-1β and IL-1α in Macrophages via a Type 1 IFN-Dependent Mechanism.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Regulator of calcineurin 1 differentially regulates TLR-dependent MyD88 and TRIF signaling pathways.PloS one · 2018Article
- BCL6 attenuates renal inflammation via negative regulation of NLRP3 transcription.Cell death & disease · 2017Article
- ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction.PLoS pathogens · 2017Article
- Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy.Chinese medical journal · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors 3 and 4 utilize adaptor TRIF to activate interferon regulatory factor 3 (IRF3), resulting in IFN-β production to mediate anti-viral and bacterial infection. Peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-activated transcription factor expressed in various immune cells and acts as a transcriptional repressor to inhibit the transcription of many proinflammatory cytokines. But, the function of PPAR-γ in TLR3- and -4-mediated IFN-β production is not well elucidated. Here, we have analyzed the effect of the PPAR-γ agonists on IFN-β production in peritoneal primary macrophages in response to LPS and poly(I:C). PPAR-γ agonists inhibited LPS and poly(I:C)-induced IFN-β transcription and secretion. siRNA knockdown of PPAR-γ expression and transfection of PPAR-γ expression plasmid demonstrated that PPAR-γ agonist inhibits IFN-β production in a PPAR-γ-dependent manner. The ability of the PPAR-γ agonist to inhibit IFN-β production was confirmed in vivo as mice treated with troglitazone exhibited decreased levels of IFN-β upon LPS and poly(I:C) challenge. Chromatin immunoprecipitation (CHIP) assay and electrophoretic mobility shift assay (EMSA) demonstrated that troglitazone treatment impaired IRF3 binding to the IFN-β promoter. Furthermore, troglitazone could inhibit LPS and poly(I:C)-induced STAT1 phosphorylation and subsequent ISRE activation. These results demonstrate that PPAR-γ negatively regulates IFN-β production in TLR3- and 4-stimulated macrophages by preventing IRF3 binding to the IFN-β promoter.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.