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• Uncontrolled inflammatory immune responses lead to a wide range of inflammatory diseases. • Macrophages based on their phenotype (M1 and M2) have a critical role in exacerbating or mitigating inflammatory disease, respectively. • Mesenchymal stem cells (MSC)-derived extracellular vesicles (EVs) offer a promising approach to inducing M2 polarization in macrophages. • Invivo-induced M2 macrophages by MSC-derived EVs ameliorate inflammation-associated diseases. Inflammation is a physiological process of the immune system, which, if it persists chronically, can contribute to inflammation-related diseases. Macrophages have a critical role in inflammation, as they undergo differentiation into M1 phenotype. One approach to managing inflammation related diseases involves the utilization of M2 macrophages and their transplantation into the host. However, the in vivo application of mediators that can induce M2 polarization faces limitations. In recent years, it has been acknowledged that extracellular vesicles originating from mesenchymal stem cells possess favorable biocompatibility, enabling their facile in vivo utilities. This study hypothesizes that MSC-derived EVs can induce M2 macrophages in vivo , then these macrophages will be used for mitigating inflammatory conditions in many clinical conditions. These vesicles exhibit the capability to enhance M2 polarization of macrophages, therefore, representing a potential therapeutic tool for modulating macrophage function in vivo , ensuring a safer application of manipulated macrophages in diseases associated with inflammation. [ABSTRACT FROM AUTHOR]

Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-β). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis. [Display omitted] • The administration of OLEU to LPS-activated macrophages leads to the reduction of harmful inflammatory responses. • The administration of OLEU to LPS-activated macrophages increases the production of anti-inflammatory cytokines. • The administration of OLEU to LPS-activated macrophages leads to the shift of responses towards the M2 phenotype. • The administration of OLEU to LPS-activated macrophages reduces the production of nitric oxide in a dose-dependent manner. • The administration of OLEU to LPS-activated macrophages can improve phagocytic activity. [ABSTRACT FROM AUTHOR]