Affiliation:
1. Department of Infections, Anhui Children’s Hospital, Hefei 230022, China
Abstract
Background::
Sepsis is a life-threatening disease caused by infection, and
developing novel strategies against sepsis is still required. Exosomes derived from
mesenchymal stem cells (MSCs) have shown promising therapeutic potential for
various diseases. In this study, we aimed to investigate the action and mechanism of
exosomes derived from IL-1β-pre-conditioned bone marrow-derived mesenchymal
stromal cells (BMSCs) in sepsis.
Methods::
Exosomes were isolated from BMSCs that were pretreated with (IL-1β-
BMSC/exos) or without IL-1β (BMSC/exos). In vitro, a cell model of sepsis was
induced by treating human umbilical vein endothelial cells (HUVECs) with
lipopolysaccharide (LPS), while in vivo, a sepsis model was established through cecal
ligation and puncture (CLP) operation. Immunofluorescence staining was used to
detect the uptake of exosomes by HUVECs. The effects of exosomes on the cellular
function of HUVECs were determined through EDU proliferation assay, migration
assay, and tube formation assay. Gene and protein expression were analyzed using
qRT-PCR, Western blot, ELISA, immunofluorescence staining, and immunohistochemistry
staining.
Results::
IL-1β-BMSC/exos significantly enhanced the proliferation, migration, and
tube formation of HUVECs. Treatment with LPS induced the expression of high
mobility group box 1 (HMGB1) and the phosphorylation of AKT in HUVECs, but these
effects were counteracted by the treatment of IL-1β-BMSC/exos. The protective effect
of IL-1β-BMSC/exos on the viability and tube formation ability of HUVECs was
reversed by overexpression of HMGB1. Moreover, IL-1β-BMSC/exos promoted the
polarization of M2 macrophages and reduced the secretion of inflammatory
chemokines. Additionally, IL-1β-BMSC/exos alleviated cecal ligation and puncture
(CLP)-induced sepsis in vivo.
Conclusion::
IL-1β-BMSC/exos alleviates sepsis by modulating the HMGB1/AKT
pathway and triggering M2 macrophage polarization.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
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