OR6-005 – Cystine crystals activate inflammasomes
نویسندگان
چکیده
Introduction Nephropathic cystinosis is a rare autosomal recessive disorder caused by a mutation in the CTNS gene, which encodes for cystinosin. It is characterized by the lysosomal accumulation of cystine, which leads to the formation of cystine crystals within various organs, including kidneys, brain, cornea, intestine and bone marrow. The exact role of intralysosomal cystine crystals accumulation in the pathogenesis of clinical features of cystinosis is still unclear, although it is well known that cystine levels are directly proportional to disease severity.
منابع مشابه
The proximal tubule in cystinosis: fight or flight?
Although rare, nephropathic cystinosis is a devastating monogenic disorder leading to renal failure in the second decade of life. Fanconi syndrome, the initial renal manifestation of cystinosis in the young child, established the proximal tubule as a primary target of injury now recognized as the result of mutations in cystinosin (CTNS), the lysosomal cystine-proton cotransporter.1 A major chal...
متن کاملCytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for rece...
متن کاملRole of Molecular Recognition in l-Cystine Crystal Growth Inhibition
l-Cystine kidney stones-aggregates of single crystals of the hexagonal form of l-cystine-afflict more than 20 000 individuals in the United States alone. Current therapies are often ineffective and produce adverse side effects. Recognizing that the growth of l-cystine crystals is a critical step in stone pathogenesis, real-time in situ atomic force microscopy of growth on the (0001) face of l-c...
متن کاملThe crystal-induced activation of NLRP3 inflammasomes in atherosclerosis
Atherosclerosis is an inflammatory disease, which is accompanied by the deposition of cholesterol-rich lipids and the infiltration of macrophages. Other well-known features of atherosclerotic lesions include the deposition of cholesterol crystals and calcium phosphate crystals; however, their pathophysiological role remains unclear. Recent studies suggest that cholesterol crystals play a pivota...
متن کاملCholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation
BACKGROUND Chronic inflammation of the arterial wall is a key element in the pathogenesis of atherosclerosis, yet the factors that trigger and sustain the inflammation remain elusive. Inflammasomes are cytoplasmic caspase-1-activating protein complexes that promote maturation and secretion of the proinflammatory cytokines interleukin(IL)-1beta and IL-18. The most intensively studied inflammasom...
متن کامل