OxLDL-induced IL-1beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation

Liu, Weiwei; Yin, Yanlin; Zhou, Ziqing; He, Ming; Dai, Yue

doi:10.1007/s00011-013-0667-3

Cited by 188 publications

(135 citation statements)

References 37 publications

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“…In the setting of ACS, it is possible that cholesterol crystals, present in atherosclerotic plaques and exposed after plaque rupture, induce inflammasome activation (5). However other factors such as the complement system (in particular C5a), TNFα (23), reactive oxygen species (24), and positive feedback from IL-1 or the inflammasome complex itself, which is released after cell apoptosis (25), may also contribute to inflammasome "priming". Indeed, the intense inflammatory milieu present in vulnerable atherosclerotic plaque might prime the inflammasome by several mechanisms, sustaining the inflammatory process.…”

Section: Increased Production Of Inflammasome-related Cytokines From mentioning

confidence: 99%

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

et al. 2016

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Rationale: Inflammasome activation, with subsequent release of pro-inflammatory cytokines IL-1β and IL-18, has recently been implicated in atherosclerosis-associated inflammation.Objective: To assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognised anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. Methods and Results:ACS patients (n=21) were randomised to oral colchicine (1 mg followed by 0.5 mg 1 hour later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre-(day 1) and 24 hours post-(day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4 % (p<0.01) in ACS patients compared to controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 vs healthy controls independent of ATP stimulation (p< 0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β vs pre-treatment levels (p<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7 % and secreted caspase-1 protein levels by 30.2 % vs untreated patients (p<0.05 for both). Conclusions:Monocytes from ACS patients are "primed" to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β. SUMMARY STATEMENTInflammasome activation in monocytes is elevated in ACS patients versus healthy subjects.Acute colchicine therapy dramatically suppresses this activation, via inhibition of caspase-1 gene transcription leading to reduced secretion of IL-1β, supporting a beneficial role for colchicine in atherosclerosis.

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Section: Increased Production Of Inflammasome-related Cytokines From mentioning

confidence: 99%

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

et al. 2016

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“…6) (120,136). Furthermore, oxLDL is involved in foam cell formation (103,116). One major source for ROS that is responsible for subendothelial oxidation processes is the NADPH oxidase complex of leukocytes, which converts O 2 into O 2 -.…”

Section: Protein Oxidation In Other Age-related Diseasesmentioning

confidence: 99%

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Reeg

Grune

2015

Antioxidants & Redox Signaling

166

134

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Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239-255.

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“…* P < 0.05, *** P < 0.001 versus control; @@ P < 0.01, @@@ P < 0.001 low Ox-LDL versus high Ox-LDL; pro-IL-1 ␤ and mature IL-1 ␤ protein expression were signifi cantly attenuated by free radical scavenger NAC and NADPH oxidase INH DPI, it is quite possible that ROS play a role in IL-1 ␤ processing. Earlier studies have also shown that free radicals mediated caspase-1 activation and IL-1 ␤ production in THP1 monocytes and macrophages after Ox-LDL stimulation ( 7,46 ).…”

Section: Discussionmentioning

confidence: 92%

“…For studying the effect of Ox-LDL on cell lines expressing higher amounts of CD36, we used PMA-differentiated THP1 cells, which express high amounts of this receptor ( 46 ) and were also used in studies such as ( 7 ). Gene silencing with TLR2-, TLR4-, TLR6-, or CD36-specifi c siRNA in THP1 monocytes and macrophages signifi cantly attenuated Ox-LDL-induced PKC ␦ and IRAK1 activation and IL-1 ␤ production, suggesting that TLR2, TLR4, TLR6, and CD36 can mediate Ox-LDL-induced effects seen in the present study.…”

Section: Discussionmentioning

confidence: 99%

PKCδ-IRAK1 axis regulates oxidized LDL-induced IL-1β production in monocytes

Tiwari

Singh

et al. 2014

Journal of Lipid Research

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OxLDL-induced IL-1beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation

Abstract: These findings suggest that oxLDL-induced NLRP3 inflammasome activation mainly depends on CD36 involved in the progression of atherosclerosis by promoting oxLDL-mediated inflammation and foam cell formation.

Cited by 188 publications

References 37 publications

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

PKCδ-IRAK1 axis regulates oxidized LDL-induced IL-1β production in monocytes

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