Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional responses of mouse bone marrow-derived macrophages (BMM) to lipopolysaccharide (LPS) - Illumina arrays

ABSTRACT: These microarrays were performed for use in a genome-wide scan for LPS-regulated genes in mouse macrophages, in order to construct a list of LPS-regulated genes for detailed interrogation on custom microarrays (see GSE19490 for custom array analysis). Mouse macrophages (bone marrow-derived macrophages, BMM) were stimulated with the TLR4 agonist, lipopolysaccharide, over a time course (0, 0.5, 2, 6, 24h) and analysed in biological duplicate by commercial Illumina microarray.

ORGANISM(S): Mus musculus

SUBMITTER: Kate Schroder

PROVIDER: E-GEOD-19766 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages.

Schroder Kate K Irvine Katharine M KM Taylor Martin S MS Bokil Nilesh J NJ Le Cao Kim-Anh KA Masterman Kelly-Anne KA Labzin Larisa I LI Semple Colin A CA Kapetanovic Ronan R Fairbairn Lynsey L Akalin Altuna A Faulkner Geoffrey J GJ Baillie John Kenneth JK Gongora Milena M Daub Carsten O CO Kawaji Hideya H McLachlan Geoffrey J GJ Goldman Nick N Grimmond Sean M SM Carninci Piero P Suzuki Harukazu H Hayashizaki Yoshihide Y Lenhard Boris B Hume David A DA Sweet Matthew J MJ

Proceedings of the National Academy of Sciences of the United States of America 20120326 16

Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)-4 agonist lipopolysaccharide (LPS). By using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5' ends, we identified extensive divergence in ...[more]

PMID: 22451944

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Project description:Interferon (IFN)γ and interleukin (IL)-4 are central regulators of T helper 1 (Th1) and T helper 2 (Th2) immune responses, respectively. Both cytokines have a major impact on macrophage phenotypes: IFNγ–priming and subsequent TLR4 activation induces so called classically activated macrophages that are characterized by pronounced pro-inflammatory responses, whereas IL-4–treated macrophages, commonly called alternatively activated, are known to develop enhanced capacity for endocytosis, antigen presentation, and tissue repair and are generally considered anti-inflammatory. Considering IL-4 as priming rather than activating stimulus, we now compared the TLR4–dependent global gene activation program in IFNγ– versus IL-4–pretreated mouse macrophages, which has rarely been studied so far. Although both cytokines frequently induced opposing effects on gene transcription, the subsequent activation of bone marrow-derived macrophages by lipopolysaccharide (LPS) produced a strong, priming dependent pro-inflammatory response in both macrophage types. For example, the production of key pro-inflammatory cytokines IL-6 and IL-12 was significantly higher in IL-4– versus IFNγ–primed macrophages and several cytokine genes, including Il19, Ccl17, Ccl22, Ccl24 and Cxcl5, were preferentially induced in alternatively primed and LPS activated mouse macrophages. In a subset of genes, including IL12a, IFNγ priming was actually found to suppress LPS–induced gene expression in a Stat1–dependent manner. Our data suggest that IL-4–priming is not per se anti-inflammatory but generates a macrophage that is “tissue protective” but still capable of mounting a strong inflammatory response after TLR4–dependent activation. Keywords: Gene expression profiling Gene expression was investigated in mouse bone marrow-derived macrophages (BMM). On day 7, BMM were stimulated with either IL-4 or IFNγ overnight (18h in total). LPS treatment was performed in primed and unprimed macrophages 4 h prior to harvesting. At least three independent experiments were performed for each condition.

Dataset Information

Transcriptional responses of mouse bone marrow-derived macrophages (BMM) to lipopolysaccharide (LPS) - Illumina arrays

Publications

Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages.

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