ArticleJournal of neuroinflammation2011
A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli.
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 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Pathological extracellular matrix changes in decellularized normal appearing gray matter and subpial multiple sclerosis lesions.iScience · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.Biomolecules · 2025Article
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- The contribution of type-I IFN-mediated neuroinflammation to Parkinson's disease progression.Brain, behavior, & immunity - health · 2025Review
- CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice.Neurobiology of disease · 2023Article
- Article
- Microglia as hackers of the matrix: sculpting synapses and the extracellular space.Cellular & molecular immunology · 2021Review
- Role of Microglia and Astrocytes in Spinal Cord Injury Induced Neuropathic Pain.Annals of neurosciences · 2021Review
- Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity.Brain sciences · 2021Article
- Connecting Neuroinflammation and Neurodegeneration in Multiple Sclerosis: Are Oligodendrocyte Precursor Cells a Nexus of Disease?Frontiers in cellular neuroscience · 2021Review
- Estrogen receptor α phosphorylated at Ser216 confers inflammatory function to mouse microglia.Cell communication and signaling : CCS · 2020Article
- Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses.Brain communications · 2020Review
- TIMP-1 Attenuates the Development of Inflammatory Pain Through MMP-Dependent and Receptor-Mediated Cell Signaling Mechanisms.Frontiers in molecular neuroscience · 2019Article
- Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity.Journal of neuroinflammation · 2017Article
- Microglia Function in the Central Nervous System During Health and Neurodegeneration.Annual review of immunology · 2017Review
- Estrogens, Neuroinflammation, and Neurodegeneration.Endocrine reviews · 2016Review
- Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models.Journal of neuroinflammation · 2016Article
- TIMP-1 couples RhoK activation to IL-1β-induced astrocyte responses.Neuroscience letters · 2015Article
- Spinal Glia Division Contributes to Conditioning Lesion-Induced Axon Regeneration Into the Injured Spinal Cord: Potential Role of Cyclic AMP-Induced Tissue Inhibitor of Metalloproteinase-1.Journal of neuropathology and experimental neurology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBy neutralizing the effect of the matrix metalloproteinases (MMPs), the tissue inhibitors of matrix metalloproteinases (TIMPs) play a critical role in maintaining tissue proteolysis in balance. As the major reactive glial cell types in the central nervous system (CNS), microglia and astrocytes play fundamental roles in mediating tissue breakdown and repair. As such, it is important to define the TIMP expression profile in these cells, as well as the mechanisms of regulation by neuroinflammatory stimuli.
methodsPrimary mixed glial cultures (MGC), pure microglia, and pure astrocytes were used in this study. To study astrocytes, we employed a recently described pure astrocyte culture system, which has the major advantage of totally lacking microglia. The three different types of culture were treated with lipopolysaccharide (LPS) or individual cytokines, and cell culture supernatants assayed for TIMP-1 or TIMP-2 protein expression by western blot.
resultsLPS induced TIMP-1 expression in MGC, but not in pure astrocyte or microglial cultures. When pure astrocytes were treated with the cytokines IL-1β, IFN-γ, TNF or TGF-β1, only IL-1β induced TIMP-1 expression. Significantly, astrocyte TIMP-1 expression was restored in LPS-treated astrocyte cultures after the addition of microglia, or conditioned medium taken from LPS-activated microglia (MG-CM). Furthermore, this effect was lost after depletion of IL-1β from MG-CM. By contrast, TIMP-2 was constitutively expressed by astrocytes, whereas microglia expressed TIMP-2 only after exposure to serum.
conclusionsTaken together, these results demonstrate an important concept in glial interactions, by showing that microglia play a central role in regulating glial cell expression of TIMPs, and identify microglial IL-1β as playing a key role in mediating microglial-astrocyte communication.
Indexed as
Identifiers
What OpenQuestion holds
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.