Endothelin-1 activates microglia

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frodo
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Endothelin-1 activates microglia

Post by frodo » Tue May 05, 2020 2:29 am

Could this be the relationship between CCSVI and MS?

Endothelin‐1 Stimulates Microglia Cells: Role in Multiple Sclerosis



Multiple Sclerosis (MS) is a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal degeneration.

There is evidence that activated microglia cells which are resident innate immune cells of the central nervous system are observed in patients with MS. These cells play an important role in inflammatory responses in part by presenting major histocompatibility complex (MHC) molecules. Elevated levels of circulating endothelin‐1 (ET‐1), a potent vasoconstrictor and important mediator of inflammatory responses, have been shown in some patients with MS and reported to induce severe and prolonged cerebral vasoconstriction.

However, the relationship between ET‐1 and microglia cell activation is unclear. We first studied a mouse model of MS –the induced experimental autoimmune encephalomyelitis (EAE) mouse. In female EAE C57BL/6 mice that were 8–12 weeks of age, we observed that ET‐1 mRNA expression by qRT‐PCR and protein levels by western blot analyses were significantly upregulated (1.5 folds ± 0.4, p<0.05, n=5) in brain tissue from EAE mice when compared to control mice. We then studied the effects of ET‐1 on HMC3, a human microglial cell line. Treatment with ET‐1 significantly increased the expression of HLA‐A [MHC class I] (5.6 folds ± 0.7, p<0.0001) and HLA‐DRA [MHC class II] (6.5 folds ± 1.4, p<0.0001) when compared to vehicle treatment. These increases were blocked by preincubation with either endothelin receptor A (ETRA) or B (ETRB) antagonists, BQ123 and BQ788, respectively (p<0.0001). In addition, ET‐1 significantly increased IL‐6 secretion from HMC3 cells by over 90% (p<0.05); an effect that was likewise sensitive to ETRA and ETRB antagonists. We also quantified Nitric Oxide (NO) production by using Griess Reagent and reactive oxygen species (ROS) production by the MUSE Oxidative Stress assay. In our cells, NO and ROS production were significantly increased by ET‐1 (p<0.05) and treatment with ETRA and ETRB blocked these effects (p<0.05).

These results suggest a novel ET‐1 pathway for activation of microglia cell inflammatory responses that may provide key information critical for our understanding of the pathophysiology of MS.

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Re: Endothelin-1 activates microglia

Post by ThisIsMA » Tue Jun 16, 2020 9:33 am

Hi Frodo, This seems like an excellent study that Joan should know about if she hasn't already seen it. I don't see a link to the study though. Can you post one? Thanks!
DX 6-09 RRMS, now SPMS

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frodo
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Re: Endothelin-1 activates microglia

Post by frodo » Fri Jun 19, 2020 1:34 am

ThisIsMA wrote:
Tue Jun 16, 2020 9:33 am
Hi Frodo, This seems like an excellent study that Joan should know about if she hasn't already seen it. I don't see a link to the study though. Can you post one? Thanks!
Sorry. Here you have it.

https://faseb.onlinelibrary.wiley.com/d ... 4.s1.02351

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