miR-511-3p limits allergic inflammation through M2 macrophage polarization and modulating CCL2 expression
Saturday, March 3, 2018: 5:45 PM
S210C (Convention Center)
Danh C. Do, PhD, , ,
RATIONALE: miR-511-3p, the active strand of miR-511, encoded by the CD206/Mrc1 has been demonstrated to reduce allergic inflammation and promote alternative (M2) macrophage polarization. We aim to elucidate the mechanism through which miR-511-3p limits allergic inflammation and induces M2 macrophage polarization.

METHODS: The effect of miR-511-3p was assessed with Mrc1-deficient (Mrc1-/-) mice using cockroach allergen (CRE)-induced mouse model of asthma and bone marrow derived macrophages (BMDMs). Microarray analysis was carried out in human (THP-1) macrophages with miR-511-3p mimic or mimic controls. Quantitation of mRNA-miRNA interaction was also assessed by biotin-labeled pulldown assay.

RESULTS: miR-511-3p delivery by adeno-associated virus (AAV) vector reduces inflammatory cells recruitment, dense peribronchial infiltrates, and goblet hyperplasia in CRE-induced mouse model of asthma. Serum and BALF analysis showed decreased CRE-specific IgG1 and IgE, with reduced Th2/Th17 cytokines (IL4, IL13, IL17A) and increased Th1/Treg (IL12, INFγ, and IL10) levels. miR-511-3p over-expression showed increased Arginase-1 (M2 marker) and decreased iNOS (M1 marker) expression in F4/80-positive lung macrophages. Microarray analysis showed that miR-511-3p mimic reduces mRNA levels of CCL2, an inducer of classically active (M1) macrophage, in THP-1 macrophages, which was confirmed in BMDMs. Furthermore, miR-511-3p-biotin pulldown showed significant enrichment of CCL2 mRNA transcripts compared to mimic controls and miR-511-3p over-expression decreases CCL2 production in BMDMs and mouse model of asthma.

CONCLUSIONS: Our studies suggested that miR-511-3p limits allergic inflammation and induces M2 polarization by modulating CCL2 expression, which may serve as a therapeutic target for allergic inflammation.