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

Autor: Laakmann K; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Eckersberg JM; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Hapke M; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Wiegand M; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Bierwagen J; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Beinborn I; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Preußer C; Institute for Tumor Immunology and Core Facility - Extracellular Vesicles, Philipps-University Marburg, Marburg, Germany., Pogge von Strandmann E; Institute for Tumor Immunology and Core Facility - Extracellular Vesicles, Philipps-University Marburg, Marburg, Germany., Heimerl T; Center for Synthetic Microbiology (SYNMIKRO), Philipps-University Marburg, Marburg, Germany., Schmeck B; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany.; Center for Synthetic Microbiology (SYNMIKRO), Philipps-University Marburg, Marburg, Germany.; Core Facility Flow Cytometry - Bacterial Vesicles, Philipps-University Marburg, Marburg, Germany.; Department of Pulmonary and Critical Care Medicine, Philipps-University Marburg, Marburg, Germany.; Member of the German Center for Infectious Disease Research (DZIF), Marburg, Germany., Jung AL; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany. anna.jung@uni-marburg.de.; Core Facility Flow Cytometry - Bacterial Vesicles, Philipps-University Marburg, Marburg, Germany. anna.jung@uni-marburg.de.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2023 May 15; Vol. 21 (1), pp. 111. Date of Electronic Publication: 2023 May 15.
DOI: 10.1186/s12964-023-01131-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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