ArticleAtherosclerosis2017
PKC-epsilon and TLR4 synergistically regulate resistin-mediated inflammation in human macrophages.
Article in Atherosclerosis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study.Journal of cancer research and clinical oncology · 2023Pooled it
- Context-dependent roles of resistin-like molecule β in mucosal defense and inflammatory diseases.Frontiers in immunology · 2026Review
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Identification of Myeloid Protein Kinase C Epsilon as a Novel Atheroprotective Gene.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Pathophysiology and emerging biomarkers of cardiovascular-renal-hepato-metabolic syndrome.Frontiers in cardiovascular medicine · 2025Review
- Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway.Scientific reports · 2024Article
- Article
- Y4 RNA fragments from cardiosphere-derived cells ameliorate diabetic myocardial ischemia‒reperfusion injury by inhibiting protein kinase C β-mediated macrophage polarization.Cardiovascular diabetology · 2024Article
- Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones.The Journal of physiology · 2023Article
- Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis-induced injury.Immunity, inflammation and disease · 2023Article
- Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion acute kidney injury and post-injury fibrosis.European journal of medical research · 2023Article
- Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis.Nutrients · 2023Article
- Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023Review
- Article
- The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications.International journal of molecular sciences · 2022Review
- Botanically-Derived ΔMolecules (Basel, Switzerland) · 2022Article
- Resistin Concentration in Early Sepsis and All-Cause Mortality at a Safety-Net Hospital in Riverside County.Journal of inflammation research · 2022Article
- MiR-140-5p inhibits oxidized low-density lipoprotein-induced oxidative stress and cell apoptosis via targeting toll-like receptor 4.Gene therapy · 2021Article
- Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis.BMC pulmonary medicine · 2021Article
- Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease.Cells · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsResistin has been associated with atherosclerotic inflammation and cardiovascular complications. We and others have previously shown that PKC-epsilon (PKCε) is involved in resistin-induced smooth muscle cell (VSMC) dysfunction at a high pathological concentration. This study aimed to evaluate the role and potential pathways of resistin at a physiological concentration, in atherosclerosis-related inflammation.
methodsPlasma from patients with atherosclerosis was analyzed for resistin concentration. Patients were divided into tertiles based on resistin levels and cytokines were compared between tertiles. Macrophages were then treated with resistin in the presence or absence of PKCε inhibitor and/or TLR4 blocking-antibody, and their inflammatory state was evaluated with ELISA, RT-PCR, immunocytochemistry, and Western blot.
resultsWe observed significant associations between plasma resistin levels and TNF-α, IL-6, IL-12, MIP-1α, MIP-1β, and CD40L. Our in vitro analyses revealed that resistin activated PKCε via TLR4. This was followed by NF-kB activation and induction of a pro-inflammatory phenotype in macrophages, significantly upregulating CD40, downregulating CD206 and stimulating gene expression and secretion of the inflammatory cytokines, for which we found association in our plasma analysis. Resistin also induced persistent TRAM and CD40L upregulation up to 36 h after resistin treatment. PKCε and TLR4 inhibitors suppressed gene expression to levels similar to control, especially when used in combination.
conclusionsResistin, at a physiological concentration, exacerbates the inflammatory response of macrophages. PKCε is a key upstream mediator in resistin-induced inflammation that may interact synergistically with TLR4 to promote NF-kB activation, while TRAM is an important signal. PKCε and TRAM may represent novel molecular targets for resistin-associated chronic atherosclerotic inflammation.
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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.