Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse classically activated and type II activated macrophages to identify novel markers

ABSTRACT: The purpose of this study is to identify novel markers for the type II activated macrophage, which is generated by classical stimulation in the presence if IgG immune complexes. These cells gererally produce high levels of IL-10 and low levels of IL-12, in comparison to classically activated macrophages. We wish to identify gene expression which is enriched in Type II activated macrophages in comparison to classically activated macrophages. Experiment Overall Design: The design of this experiment is to simulateously stimulate two popultions of macrophages and compare their gene expression. In this case, macrophages are primed overnight with IFN-gamma, washed, then stimulated with LPS (Classically) or LPS+Immune complexes (Type II).

ORGANISM(S): Mus musculus

SUBMITTER: Justin Edwards

PROVIDER: E-GEOD-4811 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Biochemical and functional characterization of three activated macrophage populations.

Edwards Justin P JP Zhang Xia X Frauwirth Kenneth A KA Mosser David M DM

Journal of leukocyte biology 20060811 6

We generated three populations of macrophages (Mphi) in vitro and characterized each. Classically activated Mphi (Ca-Mphi) were primed with IFN-gamma and stimulated with LPS. Type II-activated Mphi (Mphi-II) were similarly primed but stimulated with LPS plus immune complexes. Alternatively activated Mphi (AA-Mphi) were primed overnight with IL-4. Here, we present a side-by-side comparison of the three cell types. We focus primarily on differences between Mphi-II and AA-Mphi, as both have been cl ...[more]

PMID: 16905575

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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

Transcription profiling of mouse classically activated and type II activated macrophages to identify novel markers

Publications

Biochemical and functional characterization of three activated macrophage populations.

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