ArticleEXCLI journal2019
The mTOR kinase inhibitor rapamycin enhances the expression and release of pro-inflammatory cytokine interleukin 6 modulating the activation of human microglial cells.
Article in EXCLI journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 18 citations in OpenAlex.
- Defining the mechanisms of neuroinflammation and antepartum neuroprotection in human neural progenitor cells and microglia.AJOG global reports · 2026Article
- Review
- Drug repurposing for disease-modifying effects in multiple system atrophy.Translational neurodegeneration · 2026Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Split-Small GTPase Reassembly as a Method to Control Cellular Signaling with User-Defined Inputs.ACS chemical biology · 2025Article
- Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial.Communications medicine · 2025Article
- Immunometabolism and male reproductive function: linking inflammation, oxidative stress, and declining fertility.Frontiers in immunology · 2025Review
- α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.Tissue engineering and regenerative medicine · 2024Article
- Selection of suitable reference genes for gene expression studies in HMC3 cell line by quantitative real-time RT-PCR.Scientific reports · 2024Article
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- Remifentanil does not affect human microglial immune activation in response to pro-inflammatory cytokines.EXCLI journal · 2023Article
- Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay.STAR protocols · 2022Article
- Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.Nature communications · 2022Article
- Disease-Modifying Therapies for Multiple System Atrophy: Where Are We in 2022?Journal of Parkinson's disease · 2022Review
- SARS-CoV-2, COVID-19 and the Ageing Immune System.Nature aging · 2021Article
- Article
- SIRT1-Dependent Upregulation of BDNF in Human Microglia Challenged with Aβ: An Early but Transient Response Rescued by Melatonin.Biomedicines · 2021Article
- Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease.Cell death & disease · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence suggests the potential use of rapamycin in treatment of several neurological disorders. The drug readily crosses the blood brain barrier and may exert direct immunomodulatory effects within the brain. Microglia are the main innate immune cells of the brain, thus critically involved in the initiation and development of inflammatory processes at this level. However, there are conflicting data from rodent studies about the pharmacological effects of rapamycin on microglial inflammatory responses. Considering that rodent microglia display relevant biochemical and pharmacological differences compared to human microglia, in the present study we studied the effects of rapamycin in an experimental model of human microglia, the human microglial clone 3 (HMC3) cell line. Rapamycin was tested in the nM range both under basal conditions and in cells activated with a pro-inflammatory cytokine cocktail, consisting in a mixture of interferon-γ and interleukin-1β (II). The drug significantly increased II stimulatory effect on interleukin-6 (IL-6) expression and release in the HMC3 cells, while reducing the production of free oxygen radicals (ROS) both under basal conditions and in cells activated with II. Consistently with its known molecular mechanism of action, rapamycin reduced the extent of activation of the so-called 'mechanistic' target of rapamycin complex 1 (mTORC1) kinase and the total amount of intracellular proteins. In contrast to rodent cells, rapamycin did not alter human microglial cell viability nor inhibited cell proliferation. Moreover, rapamycin did not exert any significant effect on the morphology of the HMC3 cells. All together these data suggest that the inhibition of mTORC1 in human microglia by rapamycin results in complex immunomodulatory effects, including a significant increase in the expression and release of the pro-inflammatory IL-6.
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.