The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury

Huang, Shanshan; Che, Jing; Chu, Qian; Zhang, Peng

doi:10.3389/fcell.2020.00140

Cited by 28 publications

(14 citation statements)

References 231 publications

(195 reference statements)

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“…Upregulated NLRP3 promotes caspase-1-mediated inflammatory cascade and induces the expression of downstream proinflammatory factors, such as IL-1 β , IL-6, and TNF- α [ 24 , 36 ]. It has been reported that NLRP3 inflammasome-mediated pyroptosis is involved in exacerbating radiation-induced intestinal injury and radiation-induced cardiovascular injury [ 37 , 38 ]. Here, we demonstrated that NLRP3, caspase-1, and IL-1 β were activated in a radiation-induced mouse model of intestinal injury and cell culture model.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Huang

Wanling

et al. 2022

Oxidative Medicine and Cellular Longevity

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Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and γ-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.

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Section: Discussionmentioning

confidence: 99%

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Huang

Wanling

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Changes in external conditions can also impact the adaptation of HSPCs. For example, BM cells and hematopoiesis can be severely affected by high-dose radiotherapy [ 47 , 48 , 49 ]. The process involves a series of cellular and molecular changes, such as the depletion of hematopoietic cells, proinflammatory cytokine and chemokine release, activation and destruction of peripheral immune cells, and DNA damage [ 49 , 50 ].…”

Section: Relationship Between Inflammasomes and Hematopoiesismentioning

confidence: 99%

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Yang

et al. 2021

Molecules

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Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

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“…2 ). Necrotic cells release factors like endogenous mitochondrial damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), ATP, and IL-1α produced by stressed cells to evoke an inflammatory response [ 78 , 79 ]. These signals are sensed by the nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3), a core protein of the inflammasome.…”

Section: Pathomechanisms Of Rihdmentioning

confidence: 99%

“…NLRP3 activates and releases the pro-inflammatory cytokine IL-1β and IL-18. RT may activate NLRP3 inflammasome via multiple other mechanisms, including increased oxidative/nitrosative/nitrative stress, calcium ion influx, and potassium ion efflux [ 78 , 79 ]. NLRP3 inflammasome was suggested to play a critical role in the development of RIHD via its complex relationship with cell death and inflammatory processes [ 78 , 79 ].…”

Section: Pathomechanisms Of Rihdmentioning

confidence: 99%

Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: from bench to bedside

et al. 2021

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Cancer management has undergone significant improvements, which led to increased long-term survival rates among cancer patients. Radiotherapy (RT) has an important role in the treatment of thoracic tumors, including breast, lung, and esophageal cancer, or Hodgkin's lymphoma. RT aims to kill tumor cells; however, it may have deleterious side effects on the surrounding normal tissues. The syndrome of unwanted cardiovascular adverse effects of thoracic RT is termed radiation-induced heart disease (RIHD), and the risk of developing RIHD is a critical concern in current oncology practice. Premature ischemic heart disease, cardiomyopathy, heart failure, valve abnormalities, and electrical conduct defects are common forms of RIHD. The underlying mechanisms of RIHD are still not entirely clear, and specific therapeutic interventions are missing. In this review, we focus on the molecular pathomechanisms of acute and chronic RIHD and propose preventive measures and possible pharmacological strategies to minimize the burden of RIHD.

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The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury

Cited by 28 publications

References 231 publications

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: from bench to bedside

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