MicroRNA profiling reveals opposing expression patterns for MIR-511 in alternatively and classically activated macrophages

Background: Macrophages are heterogeneous cells, which possess pleotropic effector and immunoregulatory functions. The phenotypic diversity of macrophages is best exemplified by the ability of IL-4 or IL-13, two key cytokines in asthma to promote macrophages into a suppressive/anti-inflammatory phenotype (e.g. alternatively activated or M2) whereas exposure to IFN-γ followed by microbial trigger renders macrophages pro-inflammatory (e.g. classically activated or M1). Intriguingly, only limited data exists regarding the expression of miRNA in M2 macrophages. Objective: To define the miRNA profile of M2 and M1 macrophages. Methods: Bone marrow-derived macrophages were activated to classically and alternatively activated states using IL-4, IL-13 or IFN-γ followed by Escherichia coli stimulation. Thereafter, an unbiased miRNA "mining" approach was utilized and the expression of several miRNAs was validated following in-vitro and in-vivo macrophage activation (qPCR). miR-511 over-expression was performed followed by global transcriptional and bioinformatic analyses. Results: We report unique miRNA expression profiles in M2 and M1 macrophages involving multiple miRNAs. Among these miRNAs, we established that miR-511 is increased in macrophages following IL-4- and IL-13-stimulation and decreased in M1 macrophages both in-vitro and in-vivo. Increased miR-511 expression was sufficient to induce marked transcriptional changes in macrophages. Interestingly, bioinformatics analyses revealed that miR-511 altered the expression of gene products that are associated with hallmark alternatively activated macrophage functions, such as cellular proliferation, wound healing responses and inflammation. Conclusions: Our data establish miR-511 as a bona fide M2-associated miRNA. These data may have significant implications in asthma where the expression of IL-4 and IL-13 are highly increased.