Modulation of Macrophage Functional Polarity towards Anti-Inflammatory Phenotype with Plasmid DNA Delivery in CD44 Targeting Hyaluronic Acid Nanoparticles
| Autor: | Mansoor M. Amiji, Ruchir Rastogi, Thanh Huyen Tran, Juili Shelke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adipose tissue macrophages
Macrophage-activating factor Gene Expression Inflammation macromolecular substances Biology Transfection Article Mice immune system diseases parasitic diseases medicine Macrophage Animals Hyaluronic Acid Macrophage inflammatory protein Interleukin 4 Multidisciplinary Macrophages technology industry and agriculture hemic and immune systems Molecular biology Interleukin-10 Mice Inbred C57BL Interleukin 10 Hyaluronan Receptors Phenotype Macrophages Peritoneal Cytokines Nanoparticles Interleukin-4 medicine.symptom Inflammation Mediators CD163 Plasmids |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The purpose of this study was to modulate macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype using plasmid DNA (pDNA) expressing interleukin-4 (IL4) or interleukin-10 (IL10)-encapsulated in hyaluronic acid-poly(ethyleneimine) (HA-PEI) nanoparticles (NPs). The HA-PEI/pDNA NPs with spherical shape, average size of 186 nm were efficiently internalized by J774A.1 macrophages. Transfection of HA-PEI/pDNA-IL4 and HA-PEI/pDNA-IL10 NPs increased IL4 and IL10 gene expression in J774 macrophages which could re-program the macrophages from M1 to M2 phenotype as evidenced by a significant increase in the Arg/iNOS level and upregulation of CD206 and CD163 compared to untreated macrophages. Following intraperitoneal (IP) injection to C57BL/6 mice, HA-PEI NPs effectively targeted peritoneal macrophages over-expressing CD44 receptor. In an in vivo model of stimulated peritoneal macrophages, IP administration of HA-PEI/pDNA-IL4 and HA-PEI/pDNA-IL10 to C57BL/6 mice significantly increased the Arg/iNOS ratio and CD163 expression in the cells. Furthermore, HA-PEI/pDNA-IL10 NPs significantly increased peritoneal and serum IL10 levels which effectively suppressed LPS-induced inflammation by reducing level of TNF-α and IL-1β in peritoneal macrophages and in the peritoneal fluid. The results demonstrated that pDNA-IL10-encapsulate HA-PEI NPs skewed macrophage functional polarity from M1 toward an anti-inflammatory M2 phenotype which may be a promising platform for the treatment of inflammatory diseases. |
| Databáze: | OpenAIRE |
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