Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells

Autor: Katrin Laakmann, Jorina Mona Eckersberg, Moritz Hapke, Marie Wiegand, Jeff Bierwagen, Isabell Beinborn, Christian Preußer, Elke Pogge von Strandmann, Thomas Heimerl, Bernd Schmeck, Anna Lena Jung
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 1478-811X
DOI: 10.1186/s12964-023-01131-2
Popis: Abstract Background Sepsis is one of the leading causes of death worldwide and characterized by blood stream infections associated with a dysregulated host response and endothelial cell (EC) dysfunction. Ribonuclease 1 (RNase1) acts as a protective factor of vascular homeostasis and is known to be repressed by massive and persistent inflammation, associated to the development of vascular pathologies. Bacterial extracellular vesicles (bEVs) are released upon infection and may interact with ECs to mediate EC barrier dysfunction. Here, we investigated the impact of bEVs of sepsis-related pathogens on human EC RNase1 regulation. Methods bEVs from sepsis-associated bacteria were isolated via ultrafiltration and size exclusion chromatography and used for stimulation of human lung microvascular ECs combined with and without signaling pathway inhibitor treatments. Results bEVs from Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium significantly reduced RNase1 mRNA and protein expression and activated ECs, while TLR2-inducing bEVs from Streptococcus pneumoniae did not. These effects were mediated via LPS-dependent TLR4 signaling cascades as they could be blocked by Polymyxin B. Additionally, LPS-free ClearColi™ had no impact on RNase1. Further characterization of TLR4 downstream pathways involving NF-кB and p38, as well as JAK1/STAT1 signaling, revealed that RNase1 mRNA regulation is mediated via a p38-dependent mechanism. Conclusion Blood stream bEVs from gram-negative, sepsis-associated bacteria reduce the vascular protective factor RNase1, opening new avenues for therapeutical intervention of EC dysfunction via promotion of RNase1 integrity. Video Abstract
Databáze: Directory of Open Access Journals
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