title: miR-125a-5p regulates differential activation of macrophages and inflammation.
abstract: Macrophage activation is a central event in immune responses. Macrophages undergoing classical activation (M1 macrophages) are proinflammatory, whereas alternatively activated macrophages (M2 macrophages) are generally anti-inflammatory. miRNAs play important regulatory roles in inflammatory response. However, the manner in which miRNAs regulate macrophage activation in response to different environmental cues has not been well defined. In this study, we found that M-BMM macrophages (M2) express greater levels of miR-125a-5p than do GM-BMM macrophages (M1). Stimulation of macrophages through TLR2 and TLR4 but not through TLR3 enhanced miR-125a-5p expression. Up-regulation of miR-125a-5p after TLR2/4 activation requires the adaptor MYD88 but not TRIF. Overexpression of miR-125a-5p diminished M1 phenotype expression induced by LPS but promoted M2 marker expression induced by IL-4. In contrast, knockdown of miR-125a-5p promoted M1 polarization and diminished IL-4-induced M2 marker expression. We found that miR-125a-5p targets KLF13, a transcriptional factor that has an important role in T lymphocyte activation and inflammation. KLF13 knockdown had similar effects on M1 activation as did miR-125a-5p overexpression. In addition, miR-125a-5p regulates phagocytic and bactericidal activities of macrophages. Our data suggest that miR-125a-5p has an important role in suppressing classical activation of macrophages while promoting alternative activation.
authors.affiliation: From the Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294 and.
authors.forename: Sami
authors.initials: S
authors.lastname: Banerjee
authors.forename: Huachun
authors.initials: H
authors.lastname: Cui
authors.forename: Na
authors.initials: N
authors.lastname: Xie
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Shanzhong
authors.initials: S
authors.lastname: Yang
authors.forename: Mert
authors.initials: M
authors.lastname: Icyuz
authors.forename: Victor John
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018797:Cell Cycle Proteins; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D053594:Myeloid Differentiation Factor 88; D012097:Repressor Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C486422:Klf13 protein, mouse; C527468:Mirn125 microRNA, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse
keywords: Inflammation; KLF13; Kruppel-like Factor (KLF); Macrophage Polarization; Macrophages; MicroRNA; Phagocytosis; Toll-like Receptors (TLR)