Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation.

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

Immunity

journal_title

Immunity

authors

Sansonetti PJ,Phalipon A,Arondel J,Thirumalai K,Banerjee S,Akira S,Takeda K,Zychlinsky A

doi

10.1016/s1074-7613(00)80209-5

keywords:

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

581-90

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(00)80209-5

journal_volume

12

pub_type

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