INT81049

Context Info Confidence 0.67 First Reported 1999 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 44 Total Number 44 Disease Relevance 19.97 Pain Relevance 5.69

cytosol (CASP1) peptidase activity (CASP1) signal transduction (CASP1) intracellular (CASP1) cytoplasm (CASP1)

Anatomy Link Frequency macrophages 3 epithelial cells 2 monocytes 1 cleavage 1 CASP1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 401 99.98 addiction 35 99.88 antagonist 132 99.76 aspirin 20 99.76 Inflammatory response 32 99.36 cytokine 215 99.22 Inflammatory stimuli 24 98.80 fibrosis 85 98.68 agonist 129 98.44 chemokine 28 98.42

Disease Link Frequency Relevance Heat INFLAMMATION 467 99.98 Camurati-engelmann Disease 2 99.96 Death 136 99.92 Adenovirus Infection 2 98.94 Pulmonary Fibrosis 64 98.68 Adhesions 6 98.62 Disease 271 98.48 Toxicity 97 97.66 Syndrome 317 97.60 Apoptosis 555 97.42

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

NCX-4016, but not aspirin, prevented ICE activation as measured by assessing the release of ICE p20 subunit.

Positive_regulation (activation) of ICE associated with aspirin

1) Confidence 0.67 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.20 Pain Relevance 0.37

AEA also showed a marked increase of interleukin Ibeta- converting enzyme (ICE)CED-3 family protease (caspase-3) activity.

Positive_regulation (increase) of ICE associated with camurati-engelmann disease

2) Confidence 0.57 Published 2003 Journal Thromb. Haemost. Section Abstract Doc Link 12719786 Disease Relevance 0.85 Pain Relevance 0.21

AEA also showed a marked increase of interleukin Ibeta- converting enzyme (ICE)CED-3 family protease (caspase-3) activity.

Positive_regulation (increase) of - converting enzyme associated with camurati-engelmann disease

3) Confidence 0.49 Published 2003 Journal Thromb. Haemost. Section Abstract Doc Link 12719786 Disease Relevance 0.85 Pain Relevance 0.21

This effect is largely owing to post-translational nitrosation and therefore inactivation of cysteine proteases, such as the interleukin (IL)-1beta converting enzyme (ICE/caspase-1) involved in pro-cytokine processing.

Positive_regulation (inactivation) of ICE associated with cytokine

4) Confidence 0.49 Published 2001 Journal Trends Immunol. Section Abstract Doc Link 11323270 Disease Relevance 0.18 Pain Relevance 0.66

Caspase-1, the IL-1beta converting enzyme (ICE), is required for intracellular processing/maturation of IL-1beta and IL-18.

Positive_regulation (required) of Caspase-1

5) Confidence 0.48 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.24 Pain Relevance 0.30

This leads to activation of N-terminal domain and subsequent PYD-PYD homologous protein interaction leading to the recruitment of the ASC adaptor protein, which together with CARDINAL activates caspase-1, which, in turn cleaves pro-IL-1ß into its active form (Church et al 2008; Martinon et al 2002) (Figure 1).

Positive_regulation (activates) of caspase-1

6) Confidence 0.45 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727888 Disease Relevance 0.30 Pain Relevance 0

It has been proposed that these mutations have a gain of function effect, leading to spontaneous oligorimerization of NALP3 subunits around mutated NACHT domains and subsequent caspase-1 activation resulting in an excessive and inappropriate IL-1?

Positive_regulation (activation) of caspase-1

7) Confidence 0.42 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727888 Disease Relevance 0.63 Pain Relevance 0

When coupled with an increase in IL-1 receptor and ICE with increasing degeneration, the net effect would be the initiation and perpetuation of an IL-1-mediated response.

Positive_regulation (increase) of ICE

8) Confidence 0.41 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1175026 Disease Relevance 0.23 Pain Relevance 0.08

The precise mechanism of P2X7 receptor-induced caspase-1 activation is not clear but is known to require K+ efflux and assembly of the NALP3 inflammasome (11, 12).

Positive_regulation (activation) of caspase-1

9) Confidence 0.28 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2906308 Disease Relevance 0.39 Pain Relevance 0.17

When coupled with an increase in IL-1 receptor and ICE with increasing degeneration, the net effect would be the initiation and perpetuation of an IL-1-mediated response.

Positive_regulation (increasing) of ICE

10) Confidence 0.27 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1175026 Disease Relevance 0.23 Pain Relevance 0.08

Several mechanisms regulate the apoptotic process, such as induction of a p53-dependent-pathway after DNA-damaging agents, modulation by the bcl2 family of proteins, and activation of some effectors including the interleukin-converting enzyme (ICE) family of proteases and endonucleases [24,25].

Positive_regulation (activation) of interleukin-converting enzyme associated with apoptosis

11) Confidence 0.21 Published 2002 Journal BMC Cancer Section Body Doc Link PMC101407 Disease Relevance 0.55 Pain Relevance 0.05

production and release were investigated for dependence upon caspase-1, P2X7 receptor activation, and loss of membrane asymmetry associated with microvesicle shedding.

Positive_regulation (activation) of caspase-1 associated with addiction

12) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2906308 Disease Relevance 0.08 Pain Relevance 0.21

We show that human peripheral blood monocytes undergo PS exposure in response to P2X7 receptor activation, which was independent of priming stimulus, caspase-1 activation, and IL-1?

Positive_regulation (activation) of caspase-1 in monocytes

13) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2906308 Disease Relevance 0 Pain Relevance 0.09

We also observed that various pro-inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostaglandin E(2) and its key enzyme COX-2, not iNOS or caspase-1, were markedly up-regulated by stimulation with these TLR and NOD agonists.

Positive_regulation (up-regulated) of caspase-1 associated with chemokine, inflammatory mediators, agonist, adhesions and cytokine

14) Confidence 0.16 Published 2009 Journal J. Dent. Res. Section Abstract Doc Link 19734466 Disease Relevance 0.52 Pain Relevance 0.56

IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB.

Positive_regulation (activation) of IL-1beta-induced

15) Confidence 0.13 Published 2009 Journal Arthritis Res. Ther. Section Body Doc Link 19889203 Disease Relevance 0.06 Pain Relevance 0

expression and activation of interleukin-1 converting enzyme (caspase-1).

Positive_regulation (activation) of caspase-1

16) Confidence 0.08 Published 2006 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC1510947 Disease Relevance 0.94 Pain Relevance 0.09

expression and activation of interleukin-1 converting enzyme (caspase-1).

Positive_regulation (activation) of interleukin-1 converting enzyme

17) Confidence 0.08 Published 2006 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC1510947 Disease Relevance 0.93 Pain Relevance 0.09

The cryopyrin protein contains an N-terminal pyrin domain and has an important role in regulation of the assembly of the inflammasome, a group of proteins that when assembled activate caspase-1 that cleaves pro IL-1?

Positive_regulation (activate) of caspase-1

18) Confidence 0.08 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2880341 Disease Relevance 1.48 Pain Relevance 0.26

This results in caspase-1 activation and the subsequent processing of pro-interleukin-1-beta to its active form (Trinchieri & Sher 2007).

Positive_regulation (activation) of caspase-1

19) Confidence 0.07 Published 2007 Journal Core Evidence Section Body Doc Link PMC3012437 Disease Relevance 0.54 Pain Relevance 0.03

In addition to the role of caspases in the regulation and execution of cell death, caspase 1 (also termed IL-converting enzyme) is responsible for converting the precursors of IL-1 family cytokines IL-1?

Positive_regulation (termed) of IL-converting enzyme associated with death and cytokine

20) Confidence 0.07 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911903 Disease Relevance 0.54 Pain Relevance 0.19

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