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MicroRNA expression in thioglycollate and alternatively activated

ABSTRACT: Macrophage activation must be tightly controlled to prevent overzealous responses that cause self-damage. MicroRNAs have been shown to promote classical macrophage activation by blocking concomitant anti-inflammatory signals and transcription factors, but can also place restraints on activation by preventing excessive TLR-signalling. In contrast, the microRNA profile associated with alternatively activated macrophages and their role in regulating wound-healing or anti-helminthic responses has not yet been described. Utilizing an in vivo model of alternative activation, in which adult Brugia malayi nematodes are surgically implanted in the peritoneal cavity of mice, we examined the profile of microRNA expression in these alternatively activated macrophages and compared this to alternatively activated IL-4 receptor knockout macrophages and thioglycollate elicited macrophages.

ORGANISM(S): Rattus norvegicus Mus musculus JC polyomavirus Betapolyomavirus macacae Human gammaherpesvirus 8 Murid gammaherpesvirus 4 Homo sapiens Human immunodeficiency virus 1 Human betaherpesvirus 5 Betapolyomavirus hominis Human alphaherpesvirus 1 human gammaherpesvirus 4 Murid betaherpesvirus 1

PROVIDER: GSE35047 | GEO | 2012/08/08

SECONDARY ACCESSION(S): PRJNA150857

REPOSITORIES: GEO

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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.

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MicroRNA expression in thioglycollate and alternatively activated

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