ArticleToxicological sciences : an official journal of the Society of Toxicology2019
HMGB1-RAGE Signaling Plays a Role in Organic Dust-Induced Microglial Activation and Neuroinflammation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- The pivotal role of inflammatory factors in glaucoma: a systematic review.Frontiers in immunology · 2025Pooled it
- Risk Factors for Brain Health in Agricultural Work: A Systematic Review.International journal of environmental research and public health · 2022Pooled it
- Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy.Histology and histopathology · 2026Review
- Mechanistic investigation of HMGB1 in an in vitro model of the trigeminovascular system under migraine-like conditions.The journal of headache and pain · 2026Article
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Kv1.3 as an upstream regulator of oxidative stress-mediated neuroinflammation following organic dust exposure in murineFrontiers in toxicology · 2026Article
- Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation.Cancer medicine · 2025Review
- Identification of significant modules and hub genes involved in hepatic encephalopathy using WGCNA.European journal of medical research · 2022Article
- Role of high mobility group box protein 1 in depression: A mechanistic and therapeutic perspective.World journal of psychiatry · 2022Review
- Effect of Aucubin-Containing Eye Drops on Tear Hyposecretion and Lacrimal Gland Damage Induced by Urban Particulate Matter in Rats.Molecules (Basel, Switzerland) · 2022Article
- Transcriptomic and ultrastructural evidence indicate that anti-HMGB1 antibodies rescue organic dust-induced mitochondrial dysfunction.Cell and tissue research · 2022Article
- The pathogenic effects of particulate matter on neurodegeneration: a review.Journal of biomedical science · 2022Review
- Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target.Frontiers in neuroscience · 2022Review
- Mitoapocynin Attenuates Organic Dust Exposure-Induced Neuroinflammation and Sensory-Motor Deficits in a Mouse Model.Frontiers in cellular neuroscience · 2022Article
- Melatonin and Microglia.International journal of molecular sciences · 2021Review
- Organic dust exposure induces stress response and mitochondrial dysfunction in monocytic cells.Histochemistry and cell biology · 2021Article
- Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models.Cell and tissue research · 2021Article
- Pre-exposure to hydrogen sulfide modulates the innate inflammatory response to organic dust.Cell and tissue research · 2021Article
- Ethyl pyruvate improves white matter remodeling in rats after traumatic brain injury.CNS neuroscience & therapeutics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Occupational exposure to contaminants in agriculture and other industries is known to cause significant respiratory ailments. The effect of organic dust on lung inflammation and tissue remodeling has been actively investigated over many years but the adverse effect of organic dust-exposure on the central vital organ brain is beginning to emerge. Brain microglial cells are a major driver of neuroinflammation upon exposure to danger signals. Therefore, we tested a hypothesis that organic dust-exposure of microglial cells induces microglial cell activation and inflammation through HMGB1-RAGE signaling. Mouse microglial cells were exposed to organic dust extract showed a time-dependent increase in cytoplasmic translocation of high-mobility group box 1 (HMGB1) from the nucleus, increased expression of receptor for advanced glycation end products (RAGE) and activation of Iba1 as compared to control cells. Organic dust also induced reactive oxygen species generation, NF-κB activation, and proinflammatory cytokine release. To establish a functional relevance of HMGB1-RAGE activation in microglia-mediated neuroinflammation, we used both pharmacological and genetic approaches involving HMGB1 translocation inhibitor ethyl pyruvate (EP), anti-HMGB1 siRNA, and NOX-inhibitor mitoapocynin. Interestingly, EP effectively reduced HMGB1 nucleocytoplasmic translocation and RAGE expression along with reactive oxygen species (ROS) generation and TNF-α and IL-6 production but not NF-κB activation. HMGB1 knockdown by siRNA also reduced both ROS and reactive nitrogen species (RNS) and IL-6 levels but not TNF-α. NOX2 inhibitor mitoapocynin significantly reduced RNS levels. Collectively, our results demonstrate that organic dust activates HMGB1-RAGE signaling axis to induce a neuroinflammatory response in microglia and that attenuation of HMGB1-RAGE activation by EP and mitoapocynin treatments or genetic knockdown can dampen the neuroinflammation.
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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.