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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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Knock down of Rcor2 in P8 and R1 astrocytes. (A)Rcor2 and (B) Interleukin 6 basal gene expression levels after transfection in P8 and R1 astrocytes of a siRNA to Rcor2 (siRcor2) using a scrambled siRNA as a control (siC). Gene expression levels were measured by real-time PCR. Mean ± standard error from three independent experiments are represented; Two-way ANOVA results are indicated as *P <0.05.
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Figure 6: Knock down of Rcor2 in P8 and R1 astrocytes. (A)Rcor2 and (B) Interleukin 6 basal gene expression levels after transfection in P8 and R1 astrocytes of a siRNA to Rcor2 (siRcor2) using a scrambled siRNA as a control (siC). Gene expression levels were measured by real-time PCR. Mean ± standard error from three independent experiments are represented; Two-way ANOVA results are indicated as *P <0.05.

Mentions: Rcor2 knock down led to a 31% and 46% decrease in its expression levels in R1 and P8 astrocytes, respectively (F(1,7) = 10.082, P = 0.016) (Figure 6A). Moreover, siRcor2 astrocytes showed increased Il6 levels in both strains with significantly higher Il6 levels in P8 compared with the R1 cells (strain: F(1,6) = 10.022, P <0.05) (Figure 6B).


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)

Knock down of Rcor2 in P8 and R1 astrocytes. (A)Rcor2 and (B) Interleukin 6 basal gene expression levels after transfection in P8 and R1 astrocytes of a siRNA to Rcor2 (siRcor2) using a scrambled siRNA as a control (siC). Gene expression levels were measured by real-time PCR. Mean ± standard error from three independent experiments are represented; Two-way ANOVA results are indicated as *P <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4128581&req=5

Figure 6: Knock down of Rcor2 in P8 and R1 astrocytes. (A)Rcor2 and (B) Interleukin 6 basal gene expression levels after transfection in P8 and R1 astrocytes of a siRNA to Rcor2 (siRcor2) using a scrambled siRNA as a control (siC). Gene expression levels were measured by real-time PCR. Mean ± standard error from three independent experiments are represented; Two-way ANOVA results are indicated as *P <0.05.
Mentions: Rcor2 knock down led to a 31% and 46% decrease in its expression levels in R1 and P8 astrocytes, respectively (F(1,7) = 10.082, P = 0.016) (Figure 6A). Moreover, siRcor2 astrocytes showed increased Il6 levels in both strains with significantly higher Il6 levels in P8 compared with the R1 cells (strain: F(1,6) = 10.022, P <0.05) (Figure 6B).

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