ArticleNeurochemical research2021
IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia.
Article in Neurochemical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.Journal of cellular biochemistry · 2022Pooled it
- Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice.Redox report : communications in free radical research · 2026Article
- Rescuing anxiety by targeting the neuronal-astrocytic iron signaling axis in male mice.Signal transduction and targeted therapy · 2026Article
- Yigongsan decoction ameliorates anemia of chronic disease by attenuating mothers against decapentaplegic homolog-signal transducer and activator of transcription 3 interaction to regulate iron homeostasis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Review
- HIF-2α induces aggravated intervertebral disc degeneration by activating the IL-6/hepcidin-FPN1 axis and promoting ferroptosis in nucleus pulposus cells.Scientific reports · 2026Article
- Article
- Intermittent oral administration of iron oxide nanoparticles modulates iron homeostasis, hematological, inflammatory, and organ-specific responses in iron-deficient rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Extracellular vesicles released from blood-brain barrier endothelial cells mediate brain iron accumulation during LPS-induced brain inflammation.The Journal of biological chemistry · 2026Article
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- The role of gut microbiota mediated ferroptosis in PCOS and the therapeutic potential of Chinese herbal medicine.Frontiers in medicine · 2026Review
- Circulating microRNA molecular signatures converge with erythroid phenotypes and iron homeostasis in pediatric tic disorders.Frontiers in psychiatry · 2026Article
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- The pathological mechanisms and potential therapeutic strategies for renal anemia.Frontiers in pharmacology · 2026Review
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism.Nutrients · 2025Review
- Inhibition of astrocyte BMP signaling alleviates neuroinflammation in experimental models of Parkinson's disease.Cell death discovery · 2025Article
- The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.Acta pharmacologica Sinica · 2025Review
- Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Implications for soluble iron accumulation, oxidative stress, and glial glutamate release in motor neuron death associated with sporadic amyotrophic lateral sclerosis.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The hormone hepcidin plays a central role in controlling iron homeostasis. Iron-mediated hepcidin synthesis is triggered via the BMP/SMAD pathway. At inflammation, mainly IL-6 pro-inflammatory cytokine mediates the regulation of hepcidin via the JAK/STAT signalling pathway. Microglial cells of the central nervous system are able to recognize a broad spectrum of pathogens via toll-like receptors and initiate inflammatory response. Although the regulation of hepcidin synthesis is well described in many tissues, little is known about the inflammation mediated hepcidin regulation in microglia. In this study, we investigated the pathways, which are involved in HAMP regulation in BV2 microglia due to inflammatory mediators and the possible relationships between the iron regulatory pathways. Our results showed that IL-6 produced by resting BV2 cells was crucial in maintaining the basal HAMP expression and hepcidin secretion. It was revealed that IL-6 neutralization decreased both STAT3 and SMAD1/5/9 phosphorylation suggesting that IL-6 proinflammatory cytokine is necessary to maintain SMAD1/5/9 activation. We revealed that IL-6 influences BMP6 and TMPRSS6 protein levels, moreover it modified TfR2 expression, as well. In this study, we revealed that BV2 microglia increased their hepcidin secretion upon IL-6 neutralization although the major regulatory pathways were inhibited. Based on our results it seems that both at inflammation and at normal condition the absence of IL-6 triggered HAMP transcription and hepcidin secretion via the NFκB pathway and possibly by the autocrine effect of TNFα cytokine on BV2 microglia.
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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.