Abstract:
:Caspases are intracellular proteases that mediate mammalian cell apoptosis. Caspase-1 (Casp-1) is a unique caspase because it activates the proinflammatory cytokines interleukin (IL)-1beta and IL-18. Shigella flexneri, the etiological agent of bacillary dysentery, induces macrophage apoptosis, which requires Casp-1 and results in the release of mature IL-1beta and IL-18. Here we show that casp-1(-/-) mice infected with S. flexneri do not develop the acute inflammation characteristic of shigellosis and are unable to resolve the bacterial infection. Using casp-1(-/-) mice supplemented with recombinant cytokines and experiments with IL-1beta(-/-) and IL-18(-/-) mice, we show that IL-1beta and IL-18 are both required to mediate inflammation in S. flexneri infections. Together, these data demonstrate the importance of Casp-1 in acute inflammation and show the different roles of its substrates, IL-1beta and IL-18, in this response.
journal_name
Immunityjournal_title
Immunityauthors
Sansonetti PJ,Phalipon A,Arondel J,Thirumalai K,Banerjee S,Akira S,Takeda K,Zychlinsky Adoi
10.1016/s1074-7613(00)80209-5keywords:
subject
Has Abstractpub_date
2000-05-01 00:00:00pages
581-90issue
5eissn
1074-7613issn
1097-4180pii
S1074-7613(00)80209-5journal_volume
12pub_type
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