Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse macrophage cell line Polysomal, free mRNP, and total cellular mRNA of before and after LPS stimulation

ABSTRACT: Bacterial lipopolysaccharide(LPS) dramatically activates macrophages. So far, dozen of papers indicated that many proinflammatory molecules are transcriptionaly regulated during response. Despite of this,translational regulation is not fully elucidated especially in a comprehensive fashion. In this series, we investigated expression profiles of translation active (polysome) inactive (free mRNP) mRNAs of a typical mouse macrophage cell line, J774.1. Moreover, we also measured total cellular RNA level as a reference. Experiment Overall Design: Triplicates for each time points are included.

ORGANISM(S): Mus musculus

SUBMITTER: Hiroshi Kitamura

PROVIDER: E-GEOD-4288 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections. Experiment Overall Design: In this study, adult and aged mice were injected intraperitoneal with sterile saline or Escherichia coli LPS (0.33 mg/kg, ~10 µg/mouse; serotype 0127:B8, Sigma). This dosage of LPS was used because it induces a mild transient sickness behavior in young adults. Mice were killed 4 h after saline or LPS injection by CO2 asphyxiation. Blood samples were collected and brains were removed, separated in half at the longitudinal fissure, frozen in liquid nitrogen, and stored (-80°C) until assaying. Total RNA was later isolated from some brain samples for microarray analysis (n=3).

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Transcription profiling of mouse macrophage cell line Polysomal, free mRNP, and total cellular mRNA of before and after LPS stimulation

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