The DOI matches its Crossref record; 81 of the 81 references it cites were found in a registry or an index.
Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways
Open accessAbstract
In neurodegenerative diseases, the inflammatory response is mediated by activated glial cells, mainly microglia, which are the resident immune cells of the central nervous system. Activated microglial cells release proinflammatory mediators and neurotoxic factors that are suspected to cause or exacerbate these diseases. We recently demonstrated that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson's disease. This effect was associated with a reduction of microglial cell activation, which suggests that doxycycline may operate primarily as an anti-inflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using lipopolysaccharide (LPS)-activated primary microglial cells in culture as a model of neuroinflammation. Doxycycline attenuated the expression of key activation markers in LPS-treated microglial cultures in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the microglial activation marker IBA-1 as well as the production of ROS, NO, and proinflammatory cytokines (TNF-α and IL-1β). In primary microglial cells, we also found that doxycycline inhibits LPS-induced p38 MAP kinase phosphorylation and NF-kB nuclear translocation. The present results indicate that the effect of doxycycline on LPS-induced microglial activation probably occurs via the modulation of p38 MAP kinase and NF-kB signaling pathways. These results support the idea that doxycycline may be useful in preventing or slowing the progression of PD and other neurodegenerative diseases that exhibit altered glia function.
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“In vitro, DOX has shown anti-inflammatory properties by interfering with p38 MAP kinase and NF-κB pathways, reducing the expression of the activated microglia marker IBA-1 and inhibiting the production of the pro-oxidant and pro-inflammatory factors ROS, nitric oxide, iNOS, cyclooxygenase-2 (COX-2), IL-1β and TNF-α [280,281,282].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [280]
In the citing paper
“In vitro, DOX has shown anti-inflammatory properties by interfering with p38 MAP kinase and NF-κB pathways, reducing the expression of the activated microglia marker IBA-1 and inhibiting the production of the pro-oxidant and pro-inflammatory factors ROS, nitric oxide, iNOS, cyclooxygenase-2 (COX-2), IL-1β and TNF-α [280,281,282].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [280]
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Metadata
- Authors
- Santa-Cecília, F. V., Socias, B., Ouidja, M. O., Sepulveda-Diaz, J. E., Acuña, L., Silva, R. L., Michel, P. P., Del-Bel, E., Cunha, T. M., & Raisman-Vozari, R.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- National University of Tucumán (AR)
- Universidade de São Paulo (BR)
- ORCID
- Venue
- Neurotoxicity Research
- Published
- 2016-01-08
- Volume
- 29
- Issue
- 4
- Pages
- 447-459
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- OpenAlex
- W2232460448
- Cited by
- 165
- References
- 81
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 12 · 2023: 15 · 2022: 31 · 2021: 29 · 2020: 17 · 2019: 13 · 2018: 14 · 2017: 12 · 2016: 2
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- MINCyT-ECOS Program (A12S02)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2011/19670-0, 2013/08216-2)
- Investissements d’avenir (ANR-10-IAIHU-06)
- Translational Research Infrastructure for Biotherapies in Neurosciences (ANR-11-INBS-0011-NeurATRIS)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- doxycycline, microglial activation, neuroinflammation, p38 MAPK, NF-κB signaling, lipopolysaccharide, Parkinson's disease, anti-inflammatory activity, Iba1, reactive oxygen species, nitric oxide, TNF-α, IL-1β, substantia nigra dopaminergic neurons, neurodegenerative diseases
- MeSH terms
- Nucleophosmin, Animals, Anti-Bacterial Agents, Brain, Calcium-Binding Proteins, Cell Survival, Cells, Cultured, Doxycycline, Drug Interactions, Glial Fibrillary Acidic Protein, Lipopolysaccharides, Microfilament Proteins, Nitric Oxide, Nuclear Proteins, Signal Transduction, Macrophage-1 Antigen, Cytokines, NF-kappa B, Reactive Oxygen Species, Microglia, p38 Mitogen-Activated Protein Kinases, Mice
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