کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1931535 1050555 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Anthrax lethal toxin activates the inflammasome in sensitive rat macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Anthrax lethal toxin activates the inflammasome in sensitive rat macrophages
چکیده انگلیسی

Anthrax lethal toxin (LT) is an important virulence factor for Bacillus anthracis. In mice, LT lyses macrophages from certain inbred strains in less than 2 h by activating the Nlrp1b inflammasome and caspase-1, while macrophages from other strains remain resistant to the toxin’s effects. We analyzed LT effects in toxin-sensitive and resistant rat macrophages to test if a similar pathway was involved in rat macrophage death. LT activates caspase-1 in rat macrophages from strains harboring LT-sensitive macrophages in a manner similar to that in toxin-sensitive murine macrophages. This activation of caspase-1 is dependent on proteasome activity, and sensitive macrophages are protected from LT’s lytic effects by lactacystin. Proteasome inhibition also delayed the death of rats in response to LT, confirming our previous data implicating the rat Nlrp1 inflammasome in animal death. Quinidine, caspase-1 inhibitors, the cathepsin B inhibitor CA-074Me, and heat shock also protected rat macrophages from LT toxicity. These data support the existence of an active functioning LT-responsive Nlrp1 inflammasome in rat macrophages. The activation of the rat Nlrp1 inflammasome is required for LT-mediated rat macrophage lysis and contributes to animal death.

Research highlights
► Anthrax lethal toxin-mediated rat macrophage death requires activation of caspase-1.
► Resistant rats with rNlrp1 alleles cannot activate caspase-1 in response to lethal toxin.
► Lethal toxin-induced rat macrophage death requires proteasome activity and is inhibited by potassium channel inhibition, cathepsin B inhibition, and heat shock.
► Proteasome inhibition delays lethal toxin-induced rat death, supporting a role for rNlrp1 and caspase-1 activation in animal susceptibility to toxin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 398, Issue 4, 6 August 2010, Pages 785–789
نویسندگان
, , , ,