Anti-inflammatory effects of extracellular vesicles from Morchella on LPS-stimulated RAW264.7 cells via the ROS-mediated p38 MAPK signaling pathway

Extracellular Vesicles

Morchella is a kind of important edible and medicinal fungi, which is rich in polysaccharides, enzymes, fatty acids, amino acids and other active components. Extracellular vesicles (EVs) have a typical membrane structure, and the vesicles contain some specific lipids, miRNAs and proteins, and their can deliver the contents to different cells to change their functions. The present study investigated whether Morchella produce extracellular vesicles and its anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW246.7 macrophages. The experimental results showed that Morchella produced extracellular vesicles and significantly reduced the production of nitric oxide (NO) and reactive oxygen species (ROS) in a model of LPS-induced inflammation. In addition, the expression of inflammatory factor-related genes such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) showed dose-dependent inhibition. Morchella extracellular vesicles also can inhibit the inflammatory response induced by LPS by inhibiting the production of ROS and reducing the phosphorylation levels of the p38 MAPK signaling pathway. These results indicate that the Morchella extracellular vesicles can be used as a potential anti-inflammatory substance in the treatment of inflammatory diseases.

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Recent Publications

Cigarette smoke (CS) represents one of the most relevant environmental risk factors for several chronic pathologies. Tissue damage caused by CS exposure is mediated, at least in part, by oxidative stress induced by its toxic and pro-oxidant components. Evidence demonstrates that extracellular vesicles (EVs) released by various cell types exposed to CS extract (CSE) are characterized by altered biochemical cargo and gained pathological properties. In the present study, we evaluated the content of oxidized proteins and phospholipid fatty acid profiles of EVs released by human bronchial epithelial BEAS-2B cells treated with CSE. This specific molecular characterization has hitherto not been performed. After confirmation that CSE reduces viability of BEAS-2B cells and elevates intracellular ROS levels, in a dose-dependent manner, we demonstrated that 24 h exposure at 1% CSE, a concentration that only slight modifies cell viability but increases ROS levels, was able to increase carbonylated protein levels in cells and released EVs. The release of oxidatively modified proteins via EVs might represent a mechanism used by cells to remove toxic proteins in order to avoid their intracellular overloading. Moreover, 1% CSE induced only few changes in the fatty acid asset in BEAS-2B cell membrane phospholipids, whereas several rearrangements were observed in EVs released by CSE-treated cells. The impact of changes in acyl chain composition of CSE-EVs accounted for the increased saturation levels of phospholipids, a membrane parameter that might influence EV stability, uptake and, at least in part, EV-mediated biological effects. The present in vitro study adds new information concerning the biochemical composition of CSE-related EVs, useful to predict their biological effects on target cells. Furthermore, the information regarding the presence of oxidized proteins and the specific membrane features of CSE-related EVs can be useful to define the utilization of circulating EVs as marker for diagnosing of CS-induced lung damage and/or CS-related diseases.

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