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Rcor2 underexpression in senescent mice: a target for inflammaging?

Alvarez-López MJ, Molina-Martínez P, Castro-Freire M, Cosín-Tomás M, Cristòfol R, Párrizas M, Escorihuela RM, Pallàs M, Sanfeliu C, Kaliman P - J Neuroinflammation (2014)

Bottom Line: The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene.Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Rosellón 149, E-08036 Barcelona, Spain. pkaliman@ub.edu.

ABSTRACT

Background: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.

Methods: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.

Results: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.

Conclusions: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

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Concomitant downregulation of Rcor2 and increased IL6 gene expression in lipopolysaccharide (LPS)-treated C6 glial cell line. (A)Rcor2 and (B) interleukin 6 gene expression after LPS stimulation (1 μg/ml) in C6 glial cells. Gene expression levels were determined by real-time PCR. Mean ± standard error from three independent experiments are represented. One-way ANOVA results are indicated as **P <0.01; ***P <0.001. (C) Partial correlation between Rcor2 and Il6 gene response after LPS treatment in C6 glial cells. P value (P) and partial correlation coefficient (ρr) are indicated.
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Figure 5: Concomitant downregulation of Rcor2 and increased IL6 gene expression in lipopolysaccharide (LPS)-treated C6 glial cell line. (A)Rcor2 and (B) interleukin 6 gene expression after LPS stimulation (1 μg/ml) in C6 glial cells. Gene expression levels were determined by real-time PCR. Mean ± standard error from three independent experiments are represented. One-way ANOVA results are indicated as **P <0.01; ***P <0.001. (C) Partial correlation between Rcor2 and Il6 gene response after LPS treatment in C6 glial cells. P value (P) and partial correlation coefficient (ρr) are indicated.

Mentions: A similar effect was found in C6 glioma cells treated with LPS. C6 cells were activated with LPS for 30 min and 1, 2, 3 and 6 hours. We found a significant reduction in Rcor2 gene expression (F(5,12) = 47.332; P <0.001) with a concomitant increase in Il6 expression in response to LPS (F(5,11) = 106.833; P <0.001) (Figure 5A and B, respectively). A significant correlation (controlling for time of exposure to LPS) was found between IL-6 and Rcor2 expression (ρr = -0.512 and P = 0.043) (Figure 5C).


Rcor2 underexpression in senescent mice: a target for inflammaging?

Alvarez-López MJ, Molina-Martínez P, Castro-Freire M, Cosín-Tomás M, Cristòfol R, Párrizas M, Escorihuela RM, Pallàs M, Sanfeliu C, Kaliman P - J Neuroinflammation (2014)

Concomitant downregulation of Rcor2 and increased IL6 gene expression in lipopolysaccharide (LPS)-treated C6 glial cell line. (A)Rcor2 and (B) interleukin 6 gene expression after LPS stimulation (1 μg/ml) in C6 glial cells. Gene expression levels were determined by real-time PCR. Mean ± standard error from three independent experiments are represented. One-way ANOVA results are indicated as **P <0.01; ***P <0.001. (C) Partial correlation between Rcor2 and Il6 gene response after LPS treatment in C6 glial cells. P value (P) and partial correlation coefficient (ρr) are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4128581&req=5

Figure 5: Concomitant downregulation of Rcor2 and increased IL6 gene expression in lipopolysaccharide (LPS)-treated C6 glial cell line. (A)Rcor2 and (B) interleukin 6 gene expression after LPS stimulation (1 μg/ml) in C6 glial cells. Gene expression levels were determined by real-time PCR. Mean ± standard error from three independent experiments are represented. One-way ANOVA results are indicated as **P <0.01; ***P <0.001. (C) Partial correlation between Rcor2 and Il6 gene response after LPS treatment in C6 glial cells. P value (P) and partial correlation coefficient (ρr) are indicated.
Mentions: A similar effect was found in C6 glioma cells treated with LPS. C6 cells were activated with LPS for 30 min and 1, 2, 3 and 6 hours. We found a significant reduction in Rcor2 gene expression (F(5,12) = 47.332; P <0.001) with a concomitant increase in Il6 expression in response to LPS (F(5,11) = 106.833; P <0.001) (Figure 5A and B, respectively). A significant correlation (controlling for time of exposure to LPS) was found between IL-6 and Rcor2 expression (ρr = -0.512 and P = 0.043) (Figure 5C).

Bottom Line: The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene.Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Rosellón 149, E-08036 Barcelona, Spain. pkaliman@ub.edu.

ABSTRACT

Background: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.

Methods: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.

Results: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.

Conclusions: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

Show MeSH
Related in: MedlinePlus