ArticleJournal of neuroinflammation2011
Reactive oxygen species drive herpes simplex virus (HSV)-1-induced proinflammatory cytokine production by murine microglia.
Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 94 citations in OpenAlex.
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- Maternal Infection Induces Neuronal Structure and Behavioural Alterations in Experimental Meningitis Rat Model.Developmental neuroscience · 2026Article
- CircRNA-encoded protein fine-tunes ROS homeostasis and engages conserved JAK-STAT antiviral defenses inJournal of virology · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- The cell-mediated adaptive immune response to herpes simplex virus type 1 encephalitis: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- HSV-1 Infection in Retinal Pigment Epithelial Cells: A Possible Contribution to Age-Related Macular Degeneration.Viruses · 2025Review
- Viruses and psychiatric disorders: We have not crossed the borderline from hypothesis to proof yet (Review).Molecular medicine reports · 2025Review
- Morusin as a drug candidate: opportunities, limitations, and the path toward clinical translation.Frontiers in pharmacology · 2025Review
- Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinflammation by inhibiting oxidative stress and NF-κB activation.Journal of ginseng research · 2024Article
- Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection.Molecular neurobiology · 2024Review
- Herpes simplex keratitis: A brief clinical overview.World journal of virology · 2024Review
- Pseudorabies virus causes splenic injury via inducing oxidative stress and apoptosis related factors in mice.Scientific reports · 2023Article
- Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.Cancer letters · 2023Article
- Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1.Acta pharmacologica Sinica · 2023Article
- Manipulation of Oxidative Stress Responses by Non-Thermal Plasma to Treat Herpes Simplex Virus Type 1 Infection and Disease.International journal of molecular sciences · 2023Review
- OGG1 inhibition suppresses African swine fever virus replication.Virologica Sinica · 2023Article
- The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract ofVaccines · 2022Article
- Pharmacological Potential of Flavonoids against Neurotropic Viruses.Pharmaceuticals (Basel, Switzerland) · 2022Review
- New Insights into the Molecular Interplay between Human Herpesviruses and Alzheimer's Disease-A Narrative Review.Brain sciences · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProduction of reactive oxygen species (ROS) and proinflammatory cytokines by microglial cells in response to viral brain infection contributes to both pathogen clearance and neuronal damage. In the present study, we examined the effect of herpes simplex virus (HSV)-1-induced, NADPH oxidase-derived ROS in activating mitogen-activated protein kinases (MAPKs) as well as driving cytokine and chemokine expression in primary murine microglia.
methodsOxidation of 2', 7'-dichlorodihydrofluorescin diacetate (H2DCFDA) was used to measure production of intracellular ROS in microglial cell cultures following viral infection. Virus-induced cytokine and chemokine mRNA and protein levels were assessed using real-time RT-PCR and ELISA, respectively. Virus-induced phosphorylation of microglial p38 and p44/42 (ERK1/2) MAPKs was visualized using Western Blot, and levels of phospho-p38 were quantified using Fast Activated Cell-based ELISA (FACE assay). Diphenyleneiodonium (DPI) and apocynin (APO), inhibitors of NADPH oxidases, were used to investigate the role of virus-induced ROS in MAPK activation and cytokine, as well as chemokine, production.
resultsLevels of intracellular ROS were found to be highly elevated in primary murine microglial cells following infection with HSV and the majority of this virus-induced ROS was blocked following DPI and APO treatment. Correspondingly, inhibition of NADPH oxidase also decreased virus-induced proinflammatory cytokine and chemokine production. In addition, microglial p38 and p44/42 MAPKs were found to be phosphorylated in response to viral infection and this activation was also blocked by inhibitors of NADPH oxidase. Finally, inhibition of either of these ROS-induced signaling pathways suppressed cytokine (TNF-α and IL-1β) production, while chemokine (CCL2 and CXCL10) induction pathways were sensitive to inhibition of p38, but not ERK1/2 MAPK.
conclusionsData presented herein demonstrate that HSV infection induces proinflammatory responses in microglia through NADPH oxidase-dependent ROS and the activation of MAPKs.
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