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Cited by 330Neuroinflammation and Neurodegeneration MechanismsMicroRNA in disease regulationInflammasome and immune disorders

The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index; 14 of the 44 sources its claims cite were checked for support.

MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response

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Iyer, Anand, Zurolo, Emanuele, Prabowo, Avanita, Fluiter, Kees, Spliet, Wim G. M., van Rijen, Peter C., Gorter, Jan A., Aronica, Eleonora·2012·PLoS ONE
DOI 10.1371/journal.pone.0044789PMC PMC3441440
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Abstract

Increasing evidence supports the involvement of microRNAs (miRNA) in the regulation of inflammation in human neurological disorders. In the present study we investigated the role of miR-146a, a key regulator of the innate immune response, in the modulation of astrocyte-mediated inflammation. Using Taqman PCR and in situ hybridization, we studied the expression of miR-146a in epilepsy-associated glioneuronal lesions which are characterized by prominent activation of the innate immune response. In addition, cultured human astrocytes were used to study the regulation of miR-146a expression in response to proinflammatory cytokines. qPCR and western blot were used to evaluate the effects of overexpression or knockdown of miR-146a on IL-1β signaling. Downstream signaling in the IL-1β pathway, as well as the expression of IL-6 and COX-2 were evaluated by western blot and ELISA. Release several cytokines was evaluated using a human magnetic multiplex cytokine assay on a Luminex® 100™/200™ platform. Increased expression of miR-146a was observed in glioneuronal lesions by Taqman PCR. MiR-146a expression in human glial cell cultures was strongly induced by IL-1β and blocked by IL-1β receptor antagonist. Modulation of miR-146a expression by transfection of astrocytes with anti-miR146a or mimic, regulated the mRNA expression levels of downstream targets of miR-146a (IRAK-1, IRAK-2 and TRAF-6) and the expression of IRAK-1 protein. In addition, the expression of IL-6 and COX-2 upon IL-1β stimulation was suppressed by increased levels of miR-146a and increased by the reduction of miR-146a. Modulation of miR-146a expression affected also the release of several cytokines such as IL-6 and TNF-α. Our observations indicate that in response to inflammatory cues, miR-146a was induced as a negative-feedback regulator of the astrocyte-mediated inflammatory response. This supports an important role of miR-146a in human neurological disorders associated with chronic inflammation and suggests that this miR may represent a novel target for therapeutic strategies.

Overview

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Written from the paper’s full text.

TL;DR

This study shows that miR-146a is upregulated in epilepsy-associated glioneuronal lesions and is induced in cultured human glial cells by IL-1β, where it acts as a negative-feedback regulator of astrocyte-mediated inflammatory signaling. Modulating miR-146a alters downstream TIR-pathway targets and IL-1β-induced inflammatory mediators.

Key findings

  • miR-146a expression was significantly increased in ganglioglioma (GG) and focal cortical dysplasia type IIb (FCD IIb) compared with control cortex by qPCR (control cortex n=6 autopsy; FCD IIb n=6; GG n=5; *P<0.05). In situ hybridization showed miR-146a was undetectable in glial cells in control grey and white matter, but was expressed in GFAP-positive reactive astrocytes and balloon cells in FCD IIb; no detectable expression was seen in HLA-DR-positive microglial/macrophage cells.
  • In U373 glioblastoma cells and human fetal astrocytes, IL-1β strongly induced miR-146a; this was blocked by IL-1 receptor antagonist. LPS induced lower miR-146a and was blocked by LPS-RS, whereas IL-6 (10 ng/ml), TNFα (1 ng/ml), and HMGB1 (40 nM) did not significantly increase miR-146a. IL-1β effects began at 0.1 ng/ml, were maximal at 1–50 ng/ml, and increased miR-146a levels were detected 16 h after exposure.
  • Transfection with miR-146a mimic reduced IL-1β-stimulated IRAK-1, IRAK-2, and TRAF-6 mRNA and IRAK-1 protein; LNA-anti-miR-146a increased IRAK-1, IRAK-2, and TRAF-6 mRNA. No significant differences in IRAK-2 and TRAF-6 proteins were observed.
  • miR-146a mimic reduced IL-1β-induced IL-6 and COX-2 mRNA and COX-2 protein, while LNA-anti-miR-146a increased them. IL-1β increased release of IL-6, IL-8, IFN-γ, IP-10, MIP-1β, G-CSF, Rantes, and TNF-α; anti-miR-146a significantly increased IL-6 and IP-10, whereas mimic significantly decreased IL-6, IL-8, G-CSF, IFN-γ, IP-10, MIP-1β, and TNF-α. MCP-1 release was reduced by miR-146a mimic (control: 1582±193 pg/ml; IL-1β: 27151±1368 pg/ml; IL-1β + miR-146a mimic: 11054±2027 pg/ml; p<0.05 vs IL-1β).

Methods

  • Human surgical epilepsy specimens included GG and FCD IIb, with autopsy control cortex and histologically normal surgical temporal neocortex as controls. miR-146a expression was assessed by Taqman qPCR and in situ hybridization, including double labeling with GFAP or HLA-DR.
  • Cultured human glial cells included the U373 glioblastoma cell line and human fetal astrocyte-enriched cultures. Cells were treated with IL-1β, LPS, IL-6, TNFα, HMGB1, IL-1Ra, or LPS-RS, and transfected with LNA-anti-miR-146a or miR-146a mimic.
  • Downstream effects were measured by qPCR, western blot, ELISA for MCP-1, and a human magnetic multiplex cytokine assay on a Luminex 100/200 platform for 16 cytokines/chemokines. Statistics used two-tailed Student’s t-test or Kruskal–Wallis with Dunn’s post hoc test; P<0.05 was significant.

Limitations

  • Stated: further investigation is needed to evaluate levels of different miR-146a targets in GG and FCD, and balloon cell function could be evaluated in a culture system. The paper also notes that miR-146a effects on multiple targets may vary by cell type and stimulus, that IL-1β-induced miR-146a levels were not sufficient to significantly reduce the studied targets, and that overexpression was required to exert an anti-inflammatory effect.
  • Evident: human tissue sample sizes were small (control cortex n=6, FCD IIb n=6, GG n=5), and much of the mechanistic work used the U373 glioblastoma cell line and fetal astrocytes rather than adult human astrocytes in situ. Some fetal astrocyte results for IRAK-2 and TRAF-6 are described as “data not shown.”

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Crossref · 10.1371/journal.pone.0044789

Cites

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Figures

Figure 1 miR-146a expression in GG and FCD type IIb. (A) Quantitative real-time PCR of miR-146a in control cortex (n = 6; autopsy), FCD type IIb (n = 6) and GG (n = 5) specimens. miR-146a expression was normalized to that of the U6B small nuclear RNA gene (rnu6b). The error bars represent SEM; statistical significance: *P<0.05 compared to control. (B–E) In situ hybridization of miR-146a expression in control (B–C) and FCD type IIb (D–E) specimens. miR-146a was expressed at low levels in neurons and undetectable in glial cells in control grey (B) and white matter (C) specimens. Panels D: FCD type IIb tissue showing miR-146a expression in glial cells (arrows; insert a); inserts (b,c) in D show colocalization (purple) of miR-146a (red) in GFAP (blue) positive astrocytes. Panel E: FCD type IIb tissue showing miR-146a expression in balloon cells (arrows). Scale bar in B: B: 80 µm. C–E: 40 µm.
Figure 1 miR-146a expression in GG and FCD type IIb. (A) Quantitative real-time PCR of miR-146a in control cortex (n = 6; autopsy), FCD type IIb (n = 6) and GG (n = 5) specimens. miR-146a expression was normalized to that of the U6B small nuclear RNA gene (rnu6b). The error bars represent SEM; statistical significance: *P<0.05 compared to control. (B–E) In situ hybridization of miR-146a expression in control (B–C) and FCD type IIb (D–E) specimens. miR-146a was expressed at low levels in neurons and undetectable in glial cells in control grey (B) and white matter (C) specimens. Panels D: FCD type IIb tissue showing miR-146a expression in glial cells (arrows; insert a); inserts (b,c) in D show colocalization (purple) of miR-146a (red) in GFAP (blue) positive astrocytes. Panel E: FCD type IIb tissue showing miR-146a expression in balloon cells (arrows). Scale bar in B: B: 80 µm. C–E: 40 µm.CC BY · PubMed Central
Figure 2 miR-146a expression levels in U373 glioblastoma cell line after exposure to IL-1β. Quantitative real-time PCR of miR-146a expression in U373 cells in culture. (A) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml) or LPS (100 ng/ml) in the presence or absence of the IL-1β receptor antagonist (IL-1ra; 1 µg/ml) or LPS-RS (10 µg/ml) respectively. (B) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml), TNFα (1 ng/ml), IL-6 (10 ng/ml), HMGB1 (40 nM alone or in the presence of IL-1β). (C) Expression levels of miR-146a 24 hours after exposure to 0.1, 1, 10 or 50 ng/ml of IL-1β. (D) Expression levels of miR-146a in U373 cells incubated for different durations (10, 30, 60 min and 6, 16, 24, 48) hours in the presence of IL-1β (10 ng/ml). Data are expressed relative to the levels observed in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control).
Figure 2 miR-146a expression levels in U373 glioblastoma cell line after exposure to IL-1β. Quantitative real-time PCR of miR-146a expression in U373 cells in culture. (A) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml) or LPS (100 ng/ml) in the presence or absence of the IL-1β receptor antagonist (IL-1ra; 1 µg/ml) or LPS-RS (10 µg/ml) respectively. (B) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml), TNFα (1 ng/ml), IL-6 (10 ng/ml), HMGB1 (40 nM alone or in the presence of IL-1β). (C) Expression levels of miR-146a 24 hours after exposure to 0.1, 1, 10 or 50 ng/ml of IL-1β. (D) Expression levels of miR-146a in U373 cells incubated for different durations (10, 30, 60 min and 6, 16, 24, 48) hours in the presence of IL-1β (10 ng/ml). Data are expressed relative to the levels observed in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control).CC BY · PubMed Central
Figure 3 miR-146a expression levels in cultured human astrocytes after exposure to IL-1β. Quantitative real-time PCR of miR-146a expression in human fetal astrocytes in culture. (A) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml) or LPS (100 ng/ml) in the presence or absence of the IL-1β receptor antagonist (IL-1ra; 1 µg/ml) or LPS-RS (10 µg/m) respectively. (B) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml), TNFα (1 ng/ml), IL-6 (10 ng/ml), HMGB1 (40 nM). (C) Expression levels of miR-146a 24 hours after to 0.1, 1, 10 or 50 ng/ml of IL-1β. (D) Expression levels of miR-146a in cells incubated for different times (10, 30, 60 min and 6, 16, 24, 48) hours in the presence of IL-1β (10 ng/ml). Data are expressed relative to the levels observed in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control).
Figure 3 miR-146a expression levels in cultured human astrocytes after exposure to IL-1β. Quantitative real-time PCR of miR-146a expression in human fetal astrocytes in culture. (A) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml) or LPS (100 ng/ml) in the presence or absence of the IL-1β receptor antagonist (IL-1ra; 1 µg/ml) or LPS-RS (10 µg/m) respectively. (B) Expression levels of miR-146a 24 hours after exposure to IL-1β (10 ng/ml), TNFα (1 ng/ml), IL-6 (10 ng/ml), HMGB1 (40 nM). (C) Expression levels of miR-146a 24 hours after to 0.1, 1, 10 or 50 ng/ml of IL-1β. (D) Expression levels of miR-146a in cells incubated for different times (10, 30, 60 min and 6, 16, 24, 48) hours in the presence of IL-1β (10 ng/ml). Data are expressed relative to the levels observed in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control).CC BY · PubMed Central
Figure 4 miR-146a expression levels after transfection with anti-miR-146a LNA or miR-146a mimic (pre-miR146a). Quantitative real-time PCR of miR-146a. (A) miR-146a expression after transfection with LNA-antimiR-146a (50 nM) in U373 cells; insert shows in green tranfected cells (B) miR-146a expression after transfection of miR-146a mimic (pre-mir-146a, 1, 25 and 50 nM). (C) miR-146a expression 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (D) miR-146a expression 24 hours after exposure to IL-1β in cultured human astrocytes transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control; **p<0.05 LNA or mimic transfected cells stimulated with IL-1β, compared to IL-1β alone).
Figure 4 miR-146a expression levels after transfection with anti-miR-146a LNA or miR-146a mimic (pre-miR146a). Quantitative real-time PCR of miR-146a. (A) miR-146a expression after transfection with LNA-antimiR-146a (50 nM) in U373 cells; insert shows in green tranfected cells (B) miR-146a expression after transfection of miR-146a mimic (pre-mir-146a, 1, 25 and 50 nM). (C) miR-146a expression 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (D) miR-146a expression 24 hours after exposure to IL-1β in cultured human astrocytes transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control; **p<0.05 LNA or mimic transfected cells stimulated with IL-1β, compared to IL-1β alone).CC BY · PubMed Central
Figure 5 Expression levels of the miR-146a targets (IRAK-1, IRAK-2 and TRAF-6) after transfection with anti-miR-146a LNA or miR-146a mimic. (A–C) Quantitative real-time PCR of IRAK-1 (A), IRAK-2 (B) and TRAF-6 (C) expression 24 hours after exposure to IL-1β in U373 glioblastoma cell line transfected with LNA-antimiR-146a (25 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (D) Quantitative real-time PCR of IRAK-1, 24 hours after exposure to IL-1β in cultured human astrocytes transfected with LNA anti-miR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (E) IRAK-1 protein expression 24 hours after exposure to IL-1β in glial cells transfected with LNA anti-miR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM); Representative immunoblot (1 control; 2, IL-1β; 3, IL-1β + LNA-antimiR-146a; 4, IL-1β + LNA-antimiR-146a scramble; 5, IL-1β + mimic; 6, IL-1β + mimic scramble) and optical density measurements. Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments (*p<0.05, compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone).
Figure 5 Expression levels of the miR-146a targets (IRAK-1, IRAK-2 and TRAF-6) after transfection with anti-miR-146a LNA or miR-146a mimic. (A–C) Quantitative real-time PCR of IRAK-1 (A), IRAK-2 (B) and TRAF-6 (C) expression 24 hours after exposure to IL-1β in U373 glioblastoma cell line transfected with LNA-antimiR-146a (25 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (D) Quantitative real-time PCR of IRAK-1, 24 hours after exposure to IL-1β in cultured human astrocytes transfected with LNA anti-miR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (E) IRAK-1 protein expression 24 hours after exposure to IL-1β in glial cells transfected with LNA anti-miR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM); Representative immunoblot (1 control; 2, IL-1β; 3, IL-1β + LNA-antimiR-146a; 4, IL-1β + LNA-antimiR-146a scramble; 5, IL-1β + mimic; 6, IL-1β + mimic scramble) and optical density measurements. Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments (*p<0.05, compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone).CC BY · PubMed Central
Figure 6 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced IL-6 and COX-2 mRNA. Quantitative real-time PCR of IL-6 (A–B) and Cox-2 (C–D). (A–B) IL-6 mRNA levels, 24 hours after exposure to IL-1β in U373 cells (A) and cultured human astrocytes (B) transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (C–D) COX-2 mRNA levels, 24 hours after exposure to IL-1β in U373 cells (C) and cultured human astrocytes (D) transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone).
Figure 6 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced IL-6 and COX-2 mRNA. Quantitative real-time PCR of IL-6 (A–B) and Cox-2 (C–D). (A–B) IL-6 mRNA levels, 24 hours after exposure to IL-1β in U373 cells (A) and cultured human astrocytes (B) transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (C–D) COX-2 mRNA levels, 24 hours after exposure to IL-1β in U373 cells (C) and cultured human astrocytes (D) transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). Data are expressed relative to the levels in unstimulated cells and are mean ± SEM from two separate experiments performed in triplicate (*p<0.05 compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone).CC BY · PubMed Central
Figure 7 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced COX-2 protein and release of HMGB1. COX-2 protein expression 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (A) Representative immunoblot and (B) densitometric analysis: values (optical density units relative to the optical density of β-actin) are mean ± SEM of two separate experiments performed and are expressed relative to the levels in unstimulated cells. (C) HMGB1 immunoblot (1 control; 2, IL-1β; 3, IL-1β + mimic; 4, IL-1β + mimic scramble; 5 mimic; 6, IL-1β + LNA-antimiR-146a; 7, IL-1β + LNA-antimiR-146a scramble 8, LNA) and densitometric analysis (D, optical density units of cellular HMGB1 relative to the optical density of β-actin). *p<0.05, compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone.
Figure 7 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced COX-2 protein and release of HMGB1. COX-2 protein expression 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (pre-mir-146a, 50 nM). (A) Representative immunoblot and (B) densitometric analysis: values (optical density units relative to the optical density of β-actin) are mean ± SEM of two separate experiments performed and are expressed relative to the levels in unstimulated cells. (C) HMGB1 immunoblot (1 control; 2, IL-1β; 3, IL-1β + mimic; 4, IL-1β + mimic scramble; 5 mimic; 6, IL-1β + LNA-antimiR-146a; 7, IL-1β + LNA-antimiR-146a scramble 8, LNA) and densitometric analysis (D, optical density units of cellular HMGB1 relative to the optical density of β-actin). *p<0.05, compared to control; **p<0.05, LNA or mimic transfected cells stimulated with IL-1β compared to IL-1β alone.CC BY · PubMed Central
Figure 8 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced release of inflammatory molecules. (A) Cytokine release 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (miR-146a mimic, 50 nM). Data are expressed relative to unstimulated control cells (mean ± SEM from three separate experiments). In comparison with IL-1ß alone, cultures stimulated with IL-1ß and transfected with LNA-anti miR-146a exhibited significant increase of IL-6 and IP-10 release, whereas transfection of glial cells with miR-146a mimic significantly decreased the levels of IL-6, IL-8, G-CSF, IFN-γ, IP-10, MIP-1β, and TNF-α (* p<0.05). LNA-anti miR-146a and miR-146a mimic alone did not significantly affect the levels of cytokines in the culture medium, compared to non treated cells.
Figure 8 Effect of anti-miR-146a LNA or miR-146a mimic upon IL-1β-induced release of inflammatory molecules. (A) Cytokine release 24 hours after exposure to IL-1β in U373 cells transfected with LNA-antimiR-146a (50 nM) or miR-146a mimic (miR-146a mimic, 50 nM). Data are expressed relative to unstimulated control cells (mean ± SEM from three separate experiments). In comparison with IL-1ß alone, cultures stimulated with IL-1ß and transfected with LNA-anti miR-146a exhibited significant increase of IL-6 and IP-10 release, whereas transfection of glial cells with miR-146a mimic significantly decreased the levels of IL-6, IL-8, G-CSF, IFN-γ, IP-10, MIP-1β, and TNF-α (* p<0.05). LNA-anti miR-146a and miR-146a mimic alone did not significantly affect the levels of cytokines in the culture medium, compared to non treated cells.CC BY · PubMed Central

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  • The paper relies on this without support.

    The regulation of miR-146a in cultured human fetal astrocytes and U373 cells by IL-1β reflects the regulation of miR-146a in astrocytes in human epilepsy-associated lesions in vivo.

    “Furthermore, we investigated the regulation of miR-146a in response to inflammatory molecules in cultured human glial cells (U373 glioblastoma cell line and human astrocytes cell cultures) and further evaluated its role in regulating TLR/IL-1R-interleukin-1 receptor-associated kinase (IRAK)-NF-κB signaling, particularly in astroglia.”

  • The paper relies on this without support.

    There is little information regarding miR-146a function in astrocytes, particularly its effect on astroglia-mediated inflammatory pathways in relation to epilepsy.

    “However, there is still little information regarding miR-146a function in astrocytes, in particular regarding the effect on astroglia mediated inflammatory pathways in relation to epilepsy.”

  • The paper relies on this without support.

    The U373 glioblastoma cell line and human fetal astrocytes in culture are adequate models of human glial cells in epileptogenic lesions for studying miR-146a-mediated inflammatory responses.

    “Since miR-146a was up-regulated in astrocytes in the epileptogenic lesions (FCD, present results; TLE [20], [21]) the expression of miR-146a was further analyzed in culture, using U373 glioblastoma cell line and human fetal astrocytes.”
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  1. [43]Iyer A, Zurolo E, Spliet WG, van Rijen PC, Baayen JC, et al (2010) Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia 51: 1763– 1773. 20345941

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Metadata

Authors
Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W. G. M., van Rijen, P. C., Gorter, J. A., & Aronica, E.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • University Medical Center Utrecht (NL)
  • Stichting Epilepsie Instellingen Nederland (NL)
Corresponding author
Aronica, Eleonora
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-09-13
Volume
7
Issue
9
Pages
e44789
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0044789
PMC
PMC3441440
OpenAlex
W2138125988
Cited by
330
References
58
Citations by year
2026: 15 · 2025: 17 · 2024: 12 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 21 · 2019: 25 · 2018: 30 · 2017: 36 · 2016: 41 · 2015: 29 · 2014: 28 · 2013: 29 · 2012: 1
FWCI
13.20
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion, cc-by)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Figshare (submittedVersion, cc-by)
Funders
  • European Commission (202167, 278486)
  • Stichting Kinderen Kankervrij
  • Hersenstichting (NEF 13-01)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
microRNA-146a, astrocytes, innate immune response, epilepsy, IL-1β signaling, IRAK1, TRAF6, interleukin-6, cyclooxygenase-2, TNF-α, negative feedback regulation, anti-inflammatory therapy
MeSH terms
Astrocytes, Brain Diseases, Epilepsy, Female, Gene Expression Regulation, Humans, Immunity, Innate, Male, Pregnancy, Signal Transduction, Interleukin-6, NF-kappa B, Receptors, Interleukin-1, Ganglioglioma, Inflammation Mediators, MicroRNAs, Cell Line, Tumor, TNF Receptor-Associated Factor 6, Toll-Like Receptors, Cyclooxygenase 2, Interleukin-1beta, Interleukin-1 Receptor-Associated Kinases, Malformations of Cortical Development, Malformations of Cortical Development, Group I

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