Biotechnology

In vivo

Biology

Phosphorylation

Proinflammatory cytokine

Chemistry

In vitro

Immunology

Ex vivo

Inflammation

NF-κB

Extracellular

IκBα

MAPK/ERK pathway

Signal transduction

Biochemistry

Pharmacology

Journal of Cellular and Molecular Medicine

Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine and primary human macrophages were pre-treated with LEVs for 24 h and then were stimulated with lipopolysaccharide (LPS). We found that pre-treatment with LEVs decreased gene and protein expression of pro-inflammatory cytokines, such as IL-6, IL1-β and TNF-α, and reduced the nuclear translocation and phosphorylation of NF-κB in LPS-stimulated murine macrophages. The inhibition of NF-κB activation was associated with the reduction in ERK1-2 phosphorylation. Furthermore, the ability of LEVs to decrease pro-inflammatory cytokines and increase anti-inflammatory molecules was confirmed ex vivo in human primary T lymphocytes. In conclusion, we demonstrated that LEVs exert anti-inflammatory effects both in vitro and ex vivo by inhibiting the ERK1-2/NF-κB signalling pathway.

Anti‐inflammatory properties of lemon‐derived extracellular vesicles are achieved through the inhibition of <scp>ERK</scp>/<scp>NF‐κB</scp> signalling pathways

Anti‐inflammatory properties of lemon‐derived extracellular vesicles are achieved through the inhibition of ERK/NF‐κB signalling pathways