Chanzyme TRPM7 Mediates Ca2+ Influx Essential f/Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis & Macrophage Activation, 2018, Desal et al

Andy · Feb 26, 2018

I think this seems to be talking about the opposite of what Griffiths University claimed to have found here, https://www.s4me.info/threads/the-c...real-and-have-discovered-a-test-for-it.1638/? Griffiths claim we don't have enough calcium going into cells, this study suggests that to drop inflammation less calcium is desired. (I could be wrong about that, better brains than mine will be able to say.)

Summary
Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to activate the production of inflammatory mediators. TLR4 recognizes lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines, often contributing to sepsis.

We report that transient receptor potential melastatin-like 7 (TRPM7), a non-selective but Ca2+-conducting ion channel, mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4 endocytosis and the subsequent activation of the transcription factor IRF3. In a parallel pathway, the Ca2+ signaling initiated by TRPM7 was also essential for the nuclear translocation of NFκB.

Consequently, TRPM7-deficient macrophages exhibited major deficits in the LPS-induced transcriptional programs in that they failed to produce IL-1β and other key pro-inflammatory cytokines. In accord with these defects, mice with myeloid-specific deletion of Trpm7 are protected from LPS-induced peritonitis. Our study highlights the importance of Ca2+ signaling in macrophage activation and identifies the ion channel TRPM7 as a central component of TLR4 signaling.
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Paywalled at http://www.cell.com/immunity/fulltext/S1074-7613(17)30527-7

Article about this study.

Summary: Researchers report new findings about the immune system could help treat inflammation in Alzheimer’s disease and could save people from deadly inflammation associated with sepsis.

Source: University of Virginia Health System.

A new discovery about the immune system may allow doctors to treat harmful inflammation that damages the brain in neurodegenerative diseases such as Alzheimer’s. It might also let doctors save patients from the potentially deadly inflammation of sepsis, a full-body infection that kills a quarter-million Americans every year.

The finding “opens up a whole new research area to look at neuroinflammation in the context of Alzheimer’s and Parkinson’s,” said lead researcher Bimal Desai, PhD, of the University of Virginia School of Medicine. “But the clinical impact will be in many, many different areas.”
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His new finding, involving important immune cells known as macrophages (and microglia), could offer a way around that. He and his team have identified a specific electrical switch, known as an ion channel, within macrophages that controls the flow of calcium into the cells. Without calcium, the cells can’t cause inflammation. By targeting this switch with tiny molecules, researchers could deny the macrophages calcium and prevent inflammation – even in the brain.
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http://neurosciencenews.com/inflammation-alzheimers-immune-system-8564/

MeSci · Feb 26, 2018

I don't think it tells us much about humans to look at mice!

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Chanzyme TRPM7 Mediates Ca2+ Influx Essential f/Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis & Macrophage Activation, 2018, Desal et al

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Chanzyme TRPM7 Mediates Ca2+ Influx Essential f/Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis & Macrophage Activation, 2018, Desal et al

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