Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge

Abstract

Microglia, the innate immune cells of the CNS, respond to brain injury by activating and modifying their morphology. Our study arises from the great interest that has been focused on blueberry (BB) for the antioxidant and pharmacological properties displayed by its components. We analyzed the influence of hydroalcoholic BB extract in resting or lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. BB exerted a protective effect against LPS-induced cytotoxicity, as indicated by cell viability. BB was also able to influence the actin cytoskeleton organization, to recover the control phenotype after LPS insult, and also to reduce LPS-driven migration. We evaluated the activity of Rho and Rac1 GTPases, which regulate both actin cytoskeletal organization and migratory capacity. LPS caused an increase in Rac1 activity, which was counteracted by BB extract. Furthermore, we demonstrated that, in the presence of BB, mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α decreased, as did the immunofluorescence signal of iNOS, whereas that of Arg-1 was increased. Taken together, our results show that, during the inflammatory response, BB extract shifts the M1 polarization towards the M2 phenotype through an actin cytoskeletal rearrangement. Based on that, we might consider BB as a nutraceutical with anti-inflammatory activities.

Anhydroexfoliamycin, a Streptomyces Secondary Metabolite, Mitigates Microglia-Driven Inflammation

“…In this sense, the present results suggest that the natural product AE could change the polarization of the microglia to the immunosuppressive phenotype since the natural compound promotes the nuclear translocation of Nrf2 rather than NF-κB. In addition, morphological changes and an increment in the cell area were observed in LPS-stimulated BV2 cells, which is a sign of M1 polarization. , The ability of AE to minimize these morphological changes, in addition to the anti-inflammatory effects shown in this study, suggests that this compound reverses the phenotype M1 toward the anti-inflammatory M2. These data are consistent with current research, demonstrating that blueberry extracts shift the phenotype of LPS-stimulated BV2 cells for the immunosuppressive M2 .…”

“…These data are consistent with current research, demonstrating that blueberry extracts shift the phenotype of LPS-stimulated BV2 cells for the immunosuppressive M2. 46 Moreover, recent studies have outlined that the induction of M2 cell activation is a promising target in the context of neurodegenerative diseases. 39 Moreover, from our results in the microglia and neuron coculture, AE is not neurotoxic.…”

“…In addition, morphological changes and an increment in the cell area were observed in LPS-stimulated BV2 cells, which is a sign of M1 polarization. 46,47 The ability of AE to minimize these morphological changes, in addition to the anti-inflammatory effects shown in this study, suggests that this compound reverses the phenotype M1 toward the antiinflammatory M2. These data are consistent with current research, demonstrating that blueberry extracts shift the phenotype of LPS-stimulated BV2 cells for the immunosuppressive M2.…”

“…When microglia are activated, in addition to releasing proinflammatory mediators, their morphology is also altered. , So it was checked if LPS causes morphological and/or cytoskeletal variations in BV2 cells. For this purpose, BV2 cells were grown in coverslips, followed by fixation and labeling with Oregon Green 514 phalloidin (green), a marker for F-actin, and with Texas Red DNase I (red), a marker for G-actin.…”

Injectable Tripeptide/Polymer Nanoparticles Supramolecular Hydrogel: A Candidate for the Treatment of Inflammatory Pathologies

“…Finally, the samples were washed with 1 mL of Milli-Q water and observed by fluorescence microscopy using a Nikon Eclipse TE2000-S epifluorescence microscope with a 20× objective lens. ImageJ software was used to calculate the area covered by the nucleus and cytoskeleton . The cell area was calculated as the sum of the nucleus area plus the cytoskeleton area by counting at least 20 cells.…”