Version 1
: Received: 11 September 2024 / Approved: 11 September 2024 / Online: 11 September 2024 (17:10:31 CEST)
How to cite:
Inostroza-Nieves, Y.; Bou, S.; Alvarado-Perez, J.; Capo-Ruiz, D.; Garcia, J.; Moliere, J. P.; Arenas, C. P. Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells. Preprints2024, 2024090918. https://doi.org/10.20944/preprints202409.0918.v1
Inostroza-Nieves, Y.; Bou, S.; Alvarado-Perez, J.; Capo-Ruiz, D.; Garcia, J.; Moliere, J. P.; Arenas, C. P. Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells. Preprints 2024, 2024090918. https://doi.org/10.20944/preprints202409.0918.v1
Inostroza-Nieves, Y.; Bou, S.; Alvarado-Perez, J.; Capo-Ruiz, D.; Garcia, J.; Moliere, J. P.; Arenas, C. P. Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells. Preprints2024, 2024090918. https://doi.org/10.20944/preprints202409.0918.v1
APA Style
Inostroza-Nieves, Y., Bou, S., Alvarado-Perez, J., Capo-Ruiz, D., Garcia, J., Moliere, J. P., & Arenas, C. P. (2024). Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells. Preprints. https://doi.org/10.20944/preprints202409.0918.v1
Chicago/Turabian Style
Inostroza-Nieves, Y., Jean P Moliere and Claudia P Arenas. 2024 "Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells" Preprints. https://doi.org/10.20944/preprints202409.0918.v1
Abstract
Microglial cells are highly specialized central nervous system (CNS) cells that can promote the inflammation and neurodegeneration seen in Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal degeneration. In MS patients, demyelination is associated with activated microglia. Endothelin-1 (ET-1) is a potent vasoconstrictor that induces severe and prolonged cerebral vasoconstriction and inflammation. However, the mechanism of how ET-1 activates a proinflammatory response in the CNS is unknown. To investigate ET-1’s role in microglia activation, HMC3 cells were treated with ET-1 in the presence or absence of endothelin receptor B antagonist, BQ788. TNFα and IL-6 levels were measured using ELISA. Nitric Oxide (NO) production was measured using Griess Reagent. Reactive oxygen species (ROS) production was measured using the MUSE Oxidative Stress kit. ET-1 increases TNFα levels by 56% (p= 0.0003) and IL-6 levels by 86% (p= 0.0111) in HMC3 cells, and it was decreased to basal levels in the presence of BQ788. NO and ROS production is induced by ET-1 (p<0.05), and treatment with BQ788 was able to decrease them. ET-1 increases STAT-1 activation by 3.5 folds compared to control (p <0.0001) in microglia cells. Moreover, to study ET-1 levels in MS, we used C57BL/6 mice brains with or without induced experimental autoimmune encephalomyelitis (EAE). The brain ET-1 levels were measured by qPCR and ELISA. We found that the ET-1 gene and protein were upregulated by 1.5 folds (p= 0.0199) in EAE mice compared to the control. These data suggest that in vitro administration of ET-1-activated microglia significantly increased inflammatory cytokine levels and NO and ROS formation. This novel mechanism of microglial cell activation will provide key information to understand MS pathogenesis.
Keywords
endothelin; inflammation; microglia; multiple sclerosis; reactive oxygen species
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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