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Overview
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Background
Ac-YVAD-CHO is a potent, specific, reversible inhibitor of caspase-1, completely blocking caspase-1 activity (99%) at the concentration of 1 μM [1].
Caspase-1 is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, the activation of which results in the processing and release of cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as pyroptosis, an immunogenic form of cell death [1].
In THP-1 cells treated with α-hemolysin, Ac-YVAD-CHO inhibited 99% of the activity induced by hemolysin at 1 μM [1]. In xanthine/xanthine-oxidase (X/XO)-treated G85R-expressing N2a cells, Ac-YVAD-CHO at 100 μM, protected G85R-expressing cells against X/XO-induced loss of cell viability, caspase-1 cleavage, and increased IL-1β secretion [2].
In toluene diisocyanate (TDI)-exposed mice, Ac-YVAD-CHO (1 mg/kg, i.n., q.d., for 7 consecutive days) effectively inhibited airway hyperresponsiveness (AHR), airway inflammation around the airways and epithelial goblet cell hyperplasia. In addition, Ac-YVAD-CHO robustly decreased the numbers of TH1/TH2 cells, and lowered levels of IL-18 and IL-1β [3].[1]. O'Brien M, Moehring D, Muñoz-Planillo R, et al. A bioluminescent caspase-1 activity assay rapidly monitors inflammasome activation in cells. Journal of Immunological Methods, 2017, 447: 1-13.
[2]. Pasinelli P, Borchelt D R, Houseweart M K, et al. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proceedings of the National Academy of Sciences of the United States of America. 1998, 95(26): 1576-15768.
[3]. Chen S, Yao L, Huang P, et al. Blockade of the NLRP3/caspase-1 axis ameliorates airway neutrophilic inflammation in a toluene diisocyanate induced murine asthma model. Toxicological Sciences, 2019, 170(2): 462-472.
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