Retinoic acid-inducible gene-I, melanoma differentiation-associated gene 5 and C-X-C motif chemokine ligand 10 are induced by a Toll-like receptor 3 agonist in human brain microvascular endothelial cells

2018 ◽  
Vol 9 (3) ◽  
pp. 189-197 ◽  
Author(s):  
Tadaatsu Imaizumi ◽  
Akine Arai ◽  
Shogo Kawaguchi ◽  
Ryo Hayakari ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Human Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Toll Like Receptor ◽  
Chemokine Ligand ◽  
Microvascular Endothelial ◽  
Inducible Gene

scholarly journals Ureaplasma Species Modulate Cytokine and Chemokine Responses in Human Brain Microvascular Endothelial Cells

2019 ◽  
Vol 20 (14) ◽  
pp. 3583 ◽  
Author(s):  
Christine Silwedel ◽  
Christian P. Speer ◽  
Axel Haarmann ◽  
Markus Fehrholz ◽  
Heike Claus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Ureaplasma Urealyticum ◽  
Microvascular Endothelial Cells ◽  
Mrna Levels ◽  
Brain Microvascular Endothelial Cells ◽  
Chemokine Ligand ◽  
Microvascular Endothelial ◽  
Ureaplasma Spp

Ureaplasma species are common colonizers of the adult genitourinary tract and often considered as low-virulence commensals. Intraamniotic Ureaplasma infections, however, facilitate chorioamnionitis and preterm birth, and cases of Ureaplasma-induced neonatal sepsis, pneumonia, and meningitis raise a growing awareness of their clinical relevance. In vitro studies are scarce but demonstrate distinct Ureaplasma-driven impacts on immune mechanisms. The current study addressed cytokine and chemokine responses upon exposure of native or lipopolysaccharide (LPS) co-stimulated human brain microvascular endothelial cells (HBMEC) to Ureaplasma urealyticum or U. parvum, using qRT-PCR, RNA sequencing, multi-analyte immunoassay, and flow cytometry. Ureaplasma exposure in native HBMEC reduced monocyte chemoattractant protein (MCP)-3 mRNA expression (p < 0.01, vs. broth). In co-stimulated HBMEC, Ureaplasma spp. attenuated LPS-evoked mRNA responses for C-X-C chemokine ligand 5, MCP-1, and MCP-3 (p < 0.05, vs. LPS) and mitigated LPS-driven interleukin (IL)-1α protein secretion, as well as IL-8 mRNA and protein responses (p < 0.05). Furthermore, Ureaplasma isolates increased C-X-C chemokine receptor 4 mRNA levels in native and LPS co-stimulated HBMEC (p < 0.05). The presented results may imply immunomodulatory capacities of Ureaplasma spp. which may ultimately promote chronic colonization and long-term neuroinflammation.

scholarly journals Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5065
Author(s):  
Tatjana Vujić ◽  
Domitille Schvartz ◽  
Anton Iliuk ◽  
Jean-Charles Sanchez
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Extracellular Vesicles ◽  
Physiological State ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Cell Of Origin ◽  
Functional Changes ◽  
Data Independent Acquisition ◽  
Microvascular Endothelial

Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these “intercellular messengers” progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.

Expression of Zinc-Finger Antiviral Protein in hCMEC/D3 Human Cerebral Microvascular Endothelial Cells: Effect of a Toll-Like Receptor 3 Agonist

2021 ◽  
pp. 1-10
Author(s):  
Mako Okudera ◽  
Minami Odawara ◽  
Masashi Arakawa ◽  
Shogo Kawaguchi ◽  
Kazuhiko Seya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Zinc Finger ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Toll Like Receptor ◽  
Antiviral Protein ◽  
Polycytidylic Acid ◽  
Microvascular Endothelial ◽  
The Brain

<b><i>Introduction:</i></b> Invasion of viruses into the brain causes viral encephalitis, which can be fatal and causes permanent brain damage. The blood-brain barrier (BBB) protects the brain by excluding harmful substances and microbes. Brain microvascular endothelial cells are important components of the BBB; however, the mechanisms of antiviral reactions in these cells have not been fully elucidated. Zinc-finger antiviral protein (ZAP) is a molecule that restricts the infection of various viruses, and there are 2 major isoforms: ZAPL and ZAPS. Toll-like receptor 3 (TLR3), a pattern-recognition receptor against viral double-stranded RNA, is implicated in antiviral innate immune reactions. The aim of this study was to investigate the expression of ZAP in cultured hCMEC/D3 human brain microvascular endothelial cells treated with an authentic TLR3 agonist polyinosinic-polycytidylic acid (poly IC). <b><i>Methods:</i></b> hCMEC/D3 cells were cultured and treated with poly IC. Expression of ZAPL and ZAPS mRNA was investigated using quantitative reverse transcription-polymerase chain reaction, and protein expression of these molecules was examined using western blotting. The role of nuclear factor-κB (NF-κB) was examined using the NF-κB inhibitor, SN50. The roles of interferon (IFN)-β, IFN regulatory factor 3 (IRF3), tripartite motif protein 25 (TRIM25), and retinoic acid-inducible gene-I (RIG-I) in poly IC-induced ZAPS expression were examined using RNA interference. Propagation of Japanese encephalitis virus (JEV) was examined using a focus-forming assay. <b><i>Results:</i></b> ZAPS mRNA and protein expression was upregulated by poly IC, whereas the change of ZAPL mRNA and protein levels was minimal. Knockdown of IRF3 or TRIM25 decreased the poly IC-induced upregulation of ZAPS, whereas knockdown of IFN-β or RIG-I did not affect ZAPS upregulation. SN50 did not affect ZAPS expression. Knockdown of ZAP enhanced JEV propagation. <b><i>Conclusion:</i></b> ZAPL and ZAPS were expressed in hCMEC/D3 cells, and ZAPS expression was upregulated by poly IC. IRF3 and TRIM25 are involved in poly IC-induced upregulation of ZAPS. ZAP may contribute to antiviral reactions in brain microvascular endothelial cells and protect the brain from invading viruses such as JEV.

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