Posted on June 7, 2019 by MFeiock
Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production
Treatment with a choline kinase inhibitor prompts immune cells to clear away damaged mitochondria, thus reducing NLRP3 inflammasome activation and preventing inflammation
In a new mouse study, researchers at University of California San Diego School of Medicine discovered a unique approach that might help treat some chronic inflammatory diseases: force cells to eliminate damaged mitochondria before they activate the NLRP3 inflammasome.
The study, published April 11, 2019 by Cell Metabolism, was led by senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology and Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases at UC San Diego School of Medicine, and first author Elsa Sanchez-Lopez, PhD, a senior postdoctoral researcher in Karin's lab.
Highlights of Study:
* LPS stimulates choline uptake and phosphorylation via CTL1 induction
* Impaired choline uptake or phosphorylation reduces mitochondrial ATP synthesis
* Reduced ATP synthesis leads to AMPK activation and induction of mitophagy
* By causing mitophagy, ChoKα inhibition prevents NLRP3-dependent inflammation
Dr. Karin is also the Project Leader of Project 1 for the UCSD Superfund Research Center in which this study was partially funded.
To read more about this research, please visit the study where it is published online in the Cell Metabolism (April 11,2019).
Sanchez-Lopez, E., Zhong, Z., Stubelius, A., Sweeney, S.R., Booshehri, L.M., Antonucci, L., Liu-Bryan, R., Lodi, A., Terkeltaub, R., Lacal, J.C., Murphy, A.N., Hoffman, H.M., Tiziani, S., Guma, M., Karin, M. Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production. Cell Metab. 2019 Jun 4;29(6):1350-1362.e7.
doi: 10.1016/j.cmet.2019.03.011 PMID: 30982734 PMCID: PMC6675591
The University of California San Diego is in the process of applying for a patent covering the use of CTL1 and/or choline kinase genetic/chemical inhibitors to treat NLRP3 inflammasome-associated diseases listing, Michael Karin and Elsa Sanchez-Lopez as inventors.
For more information, please visit the following UCSD Superfund Research Project:
UCSD Superfund Research Center - Project 1 for the UCSD Superfund Research Center
Dr. Michael Karin
Distinguished Professor of Pharmacology, Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases, American Cancer Society Research Professor at the University of California, San Diego
UCSD Superfund Research Center
University of California, San Diego
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722