Scientists at the San Diego School of Medicine California (UCSD) have found a new approach that could help treat some chronic inflammatory diseases: applying cells to eliminate damaged mitochondria before they activate the inflammation NLRP3 .
To help keep tabs on inflammation, immune cells use a molecular machine called the NLRP3 inflammation. NLRP3 is inactive in a healthy cell, but is turned on when stress or exposure to bacterial toxins is damaged to the cellopondria of the cell. However, when the inflammation becomes NLRP3 stuck in the site, it can contribute to some chronic inflammatory conditions, including gout, osteoarthritis, fatty liver disease, and Alzheimer's disease.
The study was published (“Acceptance of Colony and Modulation Modulation IL-1adh and IL-18 Production”), t Cell metabolism, t led by senior author Michael Karin, PhD, renowned pharmacology and pathology professor and chairman Ben and Wanda Hildyard for mitochic and metabolic diseases at UCSD School of Medicine, and first author Elsa Sanchez-Lopez, PhD, senior postdoctoral researcher in Laboratory Karin.
“Choline is a vitamin-like nutrient that is taken up through specific carriers and metabolized by choline kinase, which converts it to phospholine essential for the synthesis of novo phosphatidylcholine (PC), the main phospholipid cellular membrane. We found that activation of receptacles such as tolls (TLR) improves the acceptance of collagen by macrophages and microglia by induction of the colonel CTL1 carrier. Prohibit the production of CTL1 or choline phosphorylation and inflammasome activation of NLRP3 reduced and IL-1β and IL-18 production in stimulated macrophages, ”the investigators wrote.
“Mechanically, a mitochondrial lipid profile that assumes the acceptance of a column, reduces the synthesis of mitigated ATP, and the AMP-activated protein protein sensor (AMPK) was activated. By encouraging DRP1 mitochondrous recruitment, AMPK stimulates derogation, which contributes to winding NLRP3 inflammasome. Accordingly, kinase choline inhibitors made acute and chronic inflammation models were dependent on IL-1β to relieve. ”
In a 2018 study published in 2007 nature, Karin team had shown that damaged mitochondria acted the NLRP3 inflammation. The researchers also found that the inflammasome NLRP3 is deactivated when the process of mitochondria is removed with the internal waste recycling process (mitophagy).
“After that, we thought we could reduce the harmful excess inflammation by mitigating the deliberate mitigation, which would eliminate damaged mitochondria and should in turn activate inflammasome NLRP3, ”Said Karin. “But at the time we had no good way to encourage mitigation.”
Recently, Sanchez-Lopez was studying how macrophages control their adoption of choline, a nutrient that is vital for metabolism, when she discovered something that can initiate mitophagy: inhibitor of the enzyme kinase colon (ChoK). To prevent ChoK, the choline is no longer incorporated in mitacondrost films. As a result, the cells appear to have damaged the mitochondria, and cleaned them with mitigation.