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Caspase-1: is IL-1 just the tip of the ICEberg?
Denes A, Lopez-Castejon G, Brough D. Denes A, et al. Cell Death Dis. 2012 Jul 5;3(7):e338. doi: 10.1038/cddis.2012.86. Cell Death Dis. 2012. PMID: 22764097 Free PMC article. Review.
However, there is also a wealth of literature supporting a direct role for caspase-1 in non-infectious cell death processes. ...We attempt here to summarise the evidence for caspase-1 as a cell death enzyme and propose that, in addition to the processing of I …
However, there is also a wealth of literature supporting a direct role for caspase-1 in non-infectious cell death processes. . …
A rapid and transient peripheral inflammatory response precedes brain inflammation after experimental stroke.
Chapman KZ, Dale VQ, Dénes A, Bennett G, Rothwell NJ, Allan SM, McColl BW. Chapman KZ, et al. J Cereb Blood Flow Metab. 2009 Nov;29(11):1764-8. doi: 10.1038/jcbfm.2009.113. Epub 2009 Aug 5. J Cereb Blood Flow Metab. 2009. PMID: 19654587
In this study, we show that experimental stroke in mice induces a peripheral inflammatory response that peaks 4 h after stroke, and precedes the peak in brain inflammation 24 h after stroke. This peripheral response is dominated by the induction of the chemokine CXCL-1 and …
In this study, we show that experimental stroke in mice induces a peripheral inflammatory response that peaks 4 h after stroke, and p …
Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation.
Denes A, Thornton P, Rothwell NJ, Allan SM. Denes A, et al. Brain Behav Immun. 2010 Jul;24(5):708-23. doi: 10.1016/j.bbi.2009.09.010. Epub 2009 Sep 19. Brain Behav Immun. 2010. PMID: 19770034 Review.
A growing literature shows strong correlations between inflammatory status and the risk of cerebral ischaemia (CI, most commonly stroke), as well as with outcome from an ischaemic event. ...However, a greater understanding of the contribution of inflammation to CI i
A growing literature shows strong correlations between inflammatory status and the risk of cerebral ischaemia (CI, most commonly stro
Platelet interleukin-1alpha drives cerebrovascular inflammation.
Thornton P, McColl BW, Greenhalgh A, Denes A, Allan SM, Rothwell NJ. Thornton P, et al. Blood. 2010 Apr 29;115(17):3632-9. doi: 10.1182/blood-2009-11-252643. Epub 2010 Mar 3. Blood. 2010. PMID: 20200351
A neutralizing antibody to IL-1alpha (but not IL-1beta) or application of IL-1 receptor antagonist inhibited platelet-induced endothelial activation by more than 90%. ...Thus, we have identified platelets as a key source of IL-1alpha and propose that platelet activa
A neutralizing antibody to IL-1alpha (but not IL-1beta) or application of IL-1 receptor antagonist inhibited platelet-induced endothe
Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics, distribution, protection.
Greenhalgh AD, Galea J, Dénes A, Tyrrell PJ, Rothwell NJ. Greenhalgh AD, et al. Br J Pharmacol. 2010 May;160(1):153-9. doi: 10.1111/j.1476-5381.2010.00684.x. Br J Pharmacol. 2010. PMID: 20412072 Free PMC article.
Thus, we tested whether interleukin-1 receptor antagonist (IL-1RA), established as a potent inhibitor of brain injury in animals and currently in clinical development, reaches the brain via a clinically relevant administration route, in experimental stroke. ...In …
Thus, we tested whether interleukin-1 receptor antagonist (IL-1RA), established as a potent inhibitor of brain injury in animals and …
Chronic systemic infection exacerbates ischemic brain damage via a CCL5 (regulated on activation, normal T-cell expressed and secreted)-mediated proinflammatory response in mice.
Dénes A, Humphreys N, Lane TE, Grencis R, Rothwell N. Dénes A, et al. J Neurosci. 2010 Jul 28;30(30):10086-95. doi: 10.1523/JNEUROSCI.1227-10.2010. J Neurosci. 2010. PMID: 20668193 Free PMC article.
We used a well established model of gut infection (Trichuris muris) to study how chronic infection contributes to brain injury. We show that, in mice, infection that leads to a chronic Th1-polarized immune response dramatically (60%) exacerbates brain damage caused …
We used a well established model of gut infection (Trichuris muris) to study how chronic infection contributes to brain injury. We sh …
Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses.
Denes A, McColl BW, Leow-Dyke SF, Chapman KZ, Humphreys NE, Grencis RK, Allan SM, Rothwell NJ. Denes A, et al. J Cereb Blood Flow Metab. 2011 Apr;31(4):1036-50. doi: 10.1038/jcbfm.2010.198. Epub 2010 Nov 3. J Cereb Blood Flow Metab. 2011. PMID: 21045863 Free PMC article.
Stroke induces a systemic response that involves rapid activation of inflammatory cascades, followed later by immunodepression. ...We show that cerebral ischaemia induced early (4  hours) release of CXCR2-positive granulocytes from the bone marrow, which was associated wit …
Stroke induces a systemic response that involves rapid activation of inflammatory cascades, followed later by immunodepression. ...We …
Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target.
Denes A, Pinteaux E, Rothwell NJ, Allan SM. Denes A, et al. Cerebrovasc Dis. 2011;32(6):517-27. doi: 10.1159/000332205. Epub 2011 Nov 18. Cerebrovasc Dis. 2011. PMID: 22104408 Review.
The inflammatory cytokine, interleukin-1 (IL-1), plays a pivotal role in both local and systemic inflammation, and is a key driver of peripheral and central immune responses to infection or injury. Inhibition of IL-1 has beneficial effects in a variety of exp …
The inflammatory cytokine, interleukin-1 (IL-1), plays a pivotal role in both local and systemic inflammation, and is a key dr …
Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size.
Dénes A, Ferenczi S, Kovács KJ. Dénes A, et al. J Neuroinflammation. 2011 Nov 24;8:164. doi: 10.1186/1742-2094-8-164. J Neuroinflammation. 2011. PMID: 22114895 Free PMC article.
Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues.
Luheshi NM, Kovács KJ, Lopez-Castejon G, Brough D, Denes A. Luheshi NM, et al. J Neuroinflammation. 2011 Dec 29;8:186. doi: 10.1186/1742-2094-8-186. J Neuroinflammation. 2011. PMID: 22206506 Free PMC article.
BACKGROUND: Cerebral ischemia is a devastating condition in which the outcome is heavily influenced by inflammatory processes, which can augment primary injury caused by reduced blood supply. ...This adds to the growing body of evidence that IL-1α is a key mediator …
BACKGROUND: Cerebral ischemia is a devastating condition in which the outcome is heavily influenced by inflammatory processes, which …
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