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.
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.
Authors: Yufeng Zhou; Danh C Do; Faoud T Ishmael; Mario Leonardo Squadrito; Ho Man Tang; Ho Lam Tang; Man-Hsun Hsu; Lipeng Qiu; Changjun Li; Yongqing Zhang; Kevin G Becker; Mei Wan; Shau-Ku Huang; Peisong Gao Journal: J Allergy Clin Immunol Date: 2017-06-17 Impact factor: 10.793
Authors: Itay Moshkovits; Danielle Karo-Atar; Michal Itan; Hadar Reichman; Perri Rozenberg; Netali Morgenstern-Ben-Baruch; Dana Shik; Aroa Ejarque-Ortiz; Alon Y Hershko; Linjie Tian; John E Coligan; Joan Sayós; Ariel Munitz Journal: Proc Natl Acad Sci U S A Date: 2015-06-29 Impact factor: 11.205
Authors: I Moshkovits; H Reichman; D Karo-Atar; P Rozenberg; E Zigmond; Y Haberman; N Ben Baruch-Morgenstern; M Lampinen; M Carlson; M Itan; L A Denson; C Varol; A Munitz Journal: Mucosal Immunol Date: 2016-04-27 Impact factor: 7.313
Authors: S E M Heinsbroek; M L Squadrito; R Schilderink; F W Hilbers; C Verseijden; M Hofmann; A Helmke; L Boon; M E Wildenberg; J J T H Roelofs; C Y Ponsioen; C P Peters; A A Te Velde; S Gordon; M De Palma; W J de Jonge Journal: Mucosal Immunol Date: 2015-11-04 Impact factor: 7.313