Loss of sterol metabolic homeostasis triggers inflammasomes - how and why.

Curr Opin Immunol

Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. Electronic address:

Published: February 2019

Proper regulation of sterol biosynthesis is critical for eukaryotic cellular homeostasis. Cholesterol and isoprenoids serve key roles in eukaryotic cells by regulating membrane fluidity and correct localization of proteins. It is becoming increasingly appreciated that dysregulated sterol metabolism engages pathways that lead to inflammation. Of particular importance are inflammasomes, which are multiplatform protein complexes that activate caspase-1 in order to process the pro-inflammatory and pyrogenic cytokines IL-1β and IL-18. In this review, we highlight recent research that links altered sterol biosynthetic pathway activity to inflammasome activation. We discuss how clues from human genetics have led to new insights into how alterations in isoprenoid biosynthesis connect to inflammation. We also discuss new mechanisms that show how macrophage cholesterol buildup can lead to inflammasome activation.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395542PMC
http://dx.doi.org/10.1016/j.coi.2018.08.001DOI Listing

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