ArticlePloS one2012
NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Physiological relevance of autocrine melatonin signaling in pineal and extrapineal sites: a systematic review.Function (Oxford, England) · 2026Pooled it
- Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Molecular Mechanisms of cGAS-STING Axis and Mitochondrial Dysfunction-Related Diseases in Humans: A Comprehensive Review.Current neuropharmacology · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- Article
- Partners in health and disease: pineal gland and purinergic signalling.Purinergic signalling · 2025Review
- Conventional and Emerging Drug Targeting Sites in Alzheimer's Disease and the Role of Translational Informatics in its Diagnosis and Management.Current neuropharmacology · 2025Review
- The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases.Current neuropharmacology · 2025Review
- A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review).International journal of molecular medicine · 2024Review
- The Gut-Brain Axis and the Microbiome in Anxiety Disorders, Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder.Current neuropharmacology · 2024Review
- The Role and Therapeutic Potential of Melatonin in Degenerative Fundus Diseases: Diabetes Retinopathy and Age-Related Macular Degeneration.Drug design, development and therapy · 2024Review
- Review
- Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the 'Bystander' Activation of Memory CD8International journal of molecular sciences · 2023Review
- Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders.International journal of molecular sciences · 2023Article
- Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses.Exploration of targeted anti-tumor therapy · 2023Review
- Amyotrophic Lateral Sclerosis Pathoetiology and Pathophysiology: Roles of Astrocytes, Gut Microbiome, and Muscle Interactions via the Mitochondrial Melatonergic Pathway, with Disruption by Glyphosate-Based Herbicides.International journal of molecular sciences · 2022Review
- Depression Pathophysiology: Astrocyte Mitochondrial Melatonergic Pathway as Crucial Hub.International journal of molecular sciences · 2022Review
- Tumor Microenvironment and Metabolism: Role of the Mitochondrial Melatonergic Pathway in Determining Intercellular Interactions in a New Dynamic Homeostasis.International journal of molecular sciences · 2022Review
- Impact of Melatonin on RAW264.7 Macrophages during Mechanical Strain.International journal of molecular sciences · 2022Article
- Gene Expression Changes of Murine Cortex Homeostasis in Response to Sleep Deprivation Hint Dysregulated Aging-like Transcriptional Responses.Brain sciences · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-κB) induces the synthesis of melatonin by macrophages and that macrophage-synthesized melatonin modulates the function of these professional phagocytes in an autocrine manner. Expression of a DsRed2 fluorescent reporter driven by regions of the aa-nat promoter, that encodes the key enzyme involved in melatonin synthesis (arylalkylamine-N-acetyltransferase), containing one or two upstream κB binding sites in RAW 264.7 macrophage cell lines was repressed when NF-κB activity was inhibited by blocking its nuclear translocation or its DNA binding activity or by silencing the transcription of the RelA or c-Rel NF-κB subunits. Therefore, transcription of aa-nat driven by NF-κB dimers containing RelA or c-Rel subunits mediates pathogen-associated molecular patterns (PAMPs) or pro-inflammatory cytokine-induced melatonin synthesis in macrophages. Furthermore, melatonin acts in an autocrine manner to potentiate macrophage phagocytic activity, whereas luzindole, a competitive antagonist of melatonin receptors, decreases macrophage phagocytic activity. The opposing functions of NF-κB in the modulation of AA-NAT expression in pinealocytes and macrophages may represent the key mechanism for the switch in the source of melatonin from the pineal gland to immune-competent cells during the development of an inflammatory response.
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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.