Umbilical cord-derived mesenchymal stromal cells immunomodulate and restore actin dynamics and phagocytosis of LPS-activated microglia via PI3K/Akt/Rho GTPase pathway
نویسندگان
چکیده
Abstract Microglia are the immune cells in central nervous system surveying environment and reacting to various injuries. Activated microglia may cause impaired synaptic plasticity, therefore modulating restoring them neutral phenotype is crucial counteract a pro-inflammatory, neurotoxic state. In this study, we focused on elucidating whether human umbilical cord (UC) -derived mesenchymal stromal (MSCs) can exert immunomodulatory effect change of activated microglia. Primary culture was by lipopolysaccharide (LPS) co-cultured with three lots MSCs. We investigated immunomodulation, actin dynamics phagocytic capacity microglia, examined Rho GTPase as mechanism. MSCs suppressed expression IL-1β pNFκB LPS-activated conversely elevated resting-surveying lot-to-lot variation. Morphological phagocytotic analyses revealed that LPS stimulation significantly increased active GTPase, Rac1, Cdc42 levels their morphology changed amoeboid which F-actin spread ruffle formation. The spreading persisted after removal reduced phagocytosis. On other hand, MSC co-culture induced bimodal increase Rac1 Moreover, extended ruffles shrinked concentrated form an ring, thereby confirmed inhibition PI3K/Akt pathway attenuated phagocytosis restored Overall, demonstrated immunomodulated variation, GTPase.
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ژورنال
عنوان ژورنال: Cell death discovery
سال: 2021
ISSN: ['2058-7716']
DOI: https://doi.org/10.1038/s41420-021-00436-w