ArticleJournal of immunology (Baltimore, Md. : 1950)2012
TLR4-mediated AKT activation is MyD88/TRIF dependent and critical for induction of oxidative phosphorylation and mitochondrial transcription factor A in murine macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 122 citations in OpenAlex.
- Macrophage activation and invasion byJournal of oral microbiology · 2026Article
- Multi-Pathway Mechanisms of Engeletin in Ischemic Stroke: A Comprehensive Study Based on Network Pharmacology, Machine Learning, and Immune Infiltration Analysis.International journal of molecular sciences · 2025Article
- Novel Sarcoidosis Epitope Augments MHCII, CD80, and CD86 Expression and Promotes B-Cell Differentiation and IgG Production.American journal of respiratory cell and molecular biology · 2025Article
- Molecular Study from the Signaling Pathways of Four PotentialInternational journal of molecular sciences · 2025Article
- TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma.Scientific reports · 2025Article
- Immunometabolic reprogramming in macrophages infected with active and dormantInfection and immunity · 2025Article
- Syringin from Tinospora crispa downregulates pro-inflammatory mediator production through MyD88-dependent pathways in lipopolysaccharide (LPS)-induced U937 macrophages.Molecular biology reports · 2024Article
- Amorfrutin B Compromises Hypoxia/Ischemia-induced Activation of Human Microglia in a PPARγ-dependent Manner: Effects on Inflammation, Proliferation Potential, and Mitochondrial Status.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- p120-Catenin suppresses NLRP3 inflammasome activation in macrophages.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4.Heliyon · 2023Article
- An integrated toolbox to profile macrophage immunometabolism.Cell reports methods · 2022Article
- Metabolic Regulation of Macrophage Activation.Journal of innate immunity · 2022Review
- MKP-1 modulates ubiquitination/phosphorylation of TLR signaling.Life science alliance · 2021Article
- Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2021Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Long non-coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA-223 down-regulation in viral myocarditis.Journal of cellular and molecular medicine · 2020Article
- Akt1 genetic variants confer increased susceptibility to thyroid cancer.Endocrine connections · 2020Article
- Standardized ethanol extract of Tinospora crispa upregulates pro-inflammatory mediators release in LPS-primed U937 human macrophages through stimulation of MAPK, NF-κB and PI3K-Akt signaling networks.BMC complementary medicine and therapies · 2020Article
- Innate Priming of Neutrophils Potentiates Systemic Multiorgan Injury.ImmunoHorizons · 2020Article
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 4 institutions in 1 country.
Funding
Abstract
Mitochondria play a critical role in cell survival and death. Mitochondrial recovery during inflammatory processes such as sepsis is associated with cell survival. Recovery of cellular respiration, mitochondrial biogenesis, and function requires coordinated expression of transcription factors encoded by nuclear and mitochondrial genes, including mitochondrial transcription factor A (T-fam) and cytochrome c oxidase (COX, complex IV). LPS elicits strong host defenses in mammals with pronounced inflammatory responses, but also triggers activation of survival pathways such as AKT pathway. AKT/PKB is a serine/threonine protein kinase that plays an important role in cell survival, protein synthesis, and controlled inflammation in response to TLRs. Hence we investigated the role of LPS-mediated AKT activation in mitochondrial bioenergetics and function in cultured murine macrophages (B6-MCL) and bone marrow-derived macrophages. We show that LPS challenge led to increased expression of T-fam and COX subunits I and IV in a time-dependent manner through early phosphorylation of the PI3K/AKT pathway. PI3K/AKT pathway inhibitors abrogated LPS-mediated T-fam and COX induction. Lack of induction was associated with decreased ATP production, increased proinflammatory cytokines (TNF-α), NO production, and cell death. The TLR4-mediated AKT activation and mitochondrial biogenesis required activation of adaptor protein MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-β. Importantly, using a genetic approach, we show that the AKT1 isoform is pivotal in regulating mitochondrial biogenesis in response to TLR4 agonist.
Indexed as
Identifiers
What OpenQuestion holds
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.