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://dx.doi.org/10.1016/j.coi.2018.08.001 | DOI Listing |
Background: Neuroinflammation is a critical factor of Alzheimer's Disease (AD). Dysregulation of complement leads to excessive inflammation, direct damage to self-cells and propagation of injury. This is likely of particular relevance in the brain where inflammation is poorly tolerated and brain cells are vulnerable to direct damage by complement.
View Article and Find Full Text PDFImmunol Invest
January 2025
Traditional Chinese Medicine, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, Heilongjiang, China.
Objective: This study investigated the mechanism of baicalin (BIA) attenuating the inflammatory response and lung injury in mycoplasma pneumoniae pneumonia (MPP) mice.
Methods: MPP mouse models were established and then treated with BIA, azithromycin, or NLRP3 inflammasome activator. Lung wet-to-dry weight (W/D) ratio were weighed.
J Neuroinflammation
January 2025
Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai, 200233, China.
Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder worldwide, and microglia are thought to play a central role in neuroinflammatory events occurring in AD. Chemerin, an adipokine, has been implicated in inflammatory diseases and central nervous system disorders, yet its precise function on microglial response in AD remains unknown.
Methods: The APP/PS1 mice were treated with different dosages of chemerin-9 (30 and 60 µg/kg), a bioactive nonapeptide derived from chemerin, every other day for 8 weeks consecutively.
J Toxicol Sci
January 2025
Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University.
A representative surfactant, benzalkonium chloride (BAC) is used as a disinfectant, but sometimes causes serious side effects, including lung disorders such as interstitial pneumonia. However, its pathogenic mechanisms remain unexplained. In this study, we identified a novel mechanism by which BAC initiates inflammatory responses that may be responsible for its side effects.
View Article and Find Full Text PDFToxicology
January 2025
School of Life Science, Liaoning University, Shenyang, 110036, China. Electronic address:
Observational studies have shown that cadmium exposure increases the risk of cardiovascular disease, but the underlying mechanism is still unclear. Atherosclerotic plaque can cause vascular obstruction, which is important for the death from cardiovascular disease. Cell damage and monocyte adhesion are two early events in atherosclerotic plaque formation that can be induced by cadmium exposure, but the mechanism remains to be determined.
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