Autocrine IFN-I inhibits isocitrate dehydrogenase in the TCA cycle of LPS-stimulated macrophages.
In: Journal of Clinical Investigation, Jg. 129 (2019-10-01), Heft 10, S. 4239-4244
Online
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Zugriff:
Macrophage activation in response to LPS is coupled to profound metabolic changes, typified by accumulation of the TCA cycle intermediates citrate, itaconate, and succinate. We have identified that endogenous type I IFN controls the cellular citrate/α-ketoglutarate ratio and inhibits expression and activity of isocitrate dehydrogenase (IDH); and, via 13C-labeling studies, demonstrated that autocrine type I IFN controls carbon flow through IDH in LPS-activated macrophages. We also found that type I IFN-driven IL-10 contributes to inhibition of IDH activity and itaconate synthesis in LPS-stimulated macrophages. Our findings have identified the autocrine type I IFN pathway as being responsible for the inhibition of IDH in LPS-stimulated macrophages. [ABSTRACT FROM AUTHOR]
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Autocrine IFN-I inhibits isocitrate dehydrogenase in the TCA cycle of LPS-stimulated macrophages.
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Autor/in / Beteiligte Person: | De Souza, David P. ; Achuthan, Adrian ; Lee, Man K. S. ; Binger, Katrina J. ; Lee, Ming-Chin ; Davidson, Sophia ; Tull, Dedreia L. ; McConville, Malcolm J. ; Cook, Andrew D. ; Murphy, Andrew J. ; Hamilton, John A. ; Fleetwood, Andrew J. ; Lee, Man Ks |
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Zeitschrift: | Journal of Clinical Investigation, Jg. 129 (2019-10-01), Heft 10, S. 4239-4244 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0021-9738 (print) |
DOI: | 10.1172/JCI127597 |
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