Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles.
Kupffer cells
extracellular vesicles
hepatic stellate cells
inflammation
toll-like receptor 4
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
15
06
2023
received:
07
03
2023
accepted:
12
07
2023
pubmed:
9
8
2023
medline:
9
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one-directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs-derived conditioned medium (CM) was harvested from different time intervals (Day 0-2: CM-D2 and Day 5-7: CM-D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM-D2 significantly induced the inflammatory phenotype in KCs, but not CM-D7. Neither CM-D2 nor CM-D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs-derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV-depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll-like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2293-2303Subventions
Organisme : China Scholarship Council
ID : 201506210062
Organisme : China Scholarship Council
ID : 202006250036
Informations de copyright
© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.
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