2010
DOI: 10.1016/j.chom.2010.11.007
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Differential Requirement for Caspase-1 Autoproteolysis in Pathogen-Induced Cell Death and Cytokine Processing

Abstract: Summary Activation of the cysteine protease Caspase-1 is a key event in the innate immune response to infections. Synthesized as a pro-protein, Caspase-1 undergoes autoproteolysis within multi-protein complexes called inflammasomes. Activated Caspase-1 is required for proteolytic processing and release of the cytokines interleukin-1β and interleukin-18, and can also cause rapid macrophage cell death. We show that macrophage cell death and cytokine maturation in response to infection with diverse bacterial path… Show more

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Cited by 599 publications

(686 citation statements)
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“…Indeed, there is robust processing and secretion of caspase-11 in response to WT and Δ flaA Lp (Figure S2). In accordance with previous findings [26], [53], caspase-1 is absolutely required for IL-1β secretion. In contrast, we observe robust IL-1α release even in the absence of caspase-1.…”
Section: Resultssupporting
confidence: 93%
“…To test if the catalytic activity of caspase-1 is required for IL-1α secretion in response to L. pneumophila , we inhibited caspase-1 catalytic activity with the pharmacological inhibitor YVAD-cmk (YVAD). Consistent with previous studies [53], IL-1β secretion in response to L. pneumophila is substantially inhibited by YVAD. However, YVAD has no effect on IL-1α secretion, indicating that IL-1α release in response to L. pneumophila does not require caspase-1 catalytic activity (Figure 1C), as has been shown for other inflammasome activators [55].…”
Section: Resultssupporting
confidence: 92%
See 1 more Smart Citation
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…Indeed, there is robust processing and secretion of caspase-11 in response to WT and Δ flaA Lp (Figure S2). In accordance with previous findings [26], [53], caspase-1 is absolutely required for IL-1β secretion. In contrast, we observe robust IL-1α release even in the absence of caspase-1.…”
Section: Resultssupporting
confidence: 93%
“…To test if the catalytic activity of caspase-1 is required for IL-1α secretion in response to L. pneumophila , we inhibited caspase-1 catalytic activity with the pharmacological inhibitor YVAD-cmk (YVAD). Consistent with previous studies [53], IL-1β secretion in response to L. pneumophila is substantially inhibited by YVAD. However, YVAD has no effect on IL-1α secretion, indicating that IL-1α release in response to L. pneumophila does not require caspase-1 catalytic activity (Figure 1C), as has been shown for other inflammasome activators [55].…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…3 E ). In agreement with previous research ( Broz et al, 2010 ), pyroptosis, and thus GSDMD N-terminal fragment, was not observed in casp-1/11 −/− cells but was cleaved in Asc −/− cells comparably with WT cells ( Fig. 3 E ).…”
Section: Resultssupporting
confidence: 93%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…We have generated and analyzed mice expressing enzymatically inactive caspase-1 C284A , which we have named Casp1 mlt . In contrast to the previous observation that biochemical inhibition of caspase-1 by peptide-based inhibitors selectively blocks IL-1β cleavage but does not prevent pyroptosis or IL-1 secretion ( Broz et al., 2010 , Cullen et al., 2015 , Groß et al., 2012 ), genetic inactivation of caspase-1 protease activity prevented not only IL-1β cleavage but also canonical IL-1 secretion and pyroptosis at early time points after inflammasome activation. The inability of Ac-YVAD-cmk to block cleavage of the pyroptotic effector GSDMD explains this discrepancy.…”
Section: Discussioncontrasting
confidence: 98%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.