Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells

Alhaji Osman Smith,1,2 Wen Ju,1– 3 Seyram Yao Adzraku,1,2 Lu wenyi,1,2 Chen Yuting,1,2 Jianlin Qiao,1– 3 Kailin Xu,1– 3 Lingyu Zeng1– 3 1Department of Blood Diseases Institute, Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of China; 2Department of Key Laboratory...

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Autores principales:	Smith AO, Ju W, Adzraku SY, wenyi L, Yuting C, Qiao J, Xu K, Zeng L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	gamma radiation microvascular endothelial cells (ecs) nod-like receptor (nlr) inflammasome and pyroptosis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d890e705fcea4b6287e5a361d8ed0684
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spelling	oai:doaj.org-article:d890e705fcea4b6287e5a361d8ed06842021-12-02T16:11:44ZGamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells1178-7031https://doaj.org/article/d890e705fcea4b6287e5a361d8ed06842021-07-01T00:00:00Zhttps://www.dovepress.com/gamma-radiation-induce-inflammasome-signaling-and-pyroptosis-in-microv-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Alhaji Osman Smith,1,2 Wen Ju,1– 3 Seyram Yao Adzraku,1,2 Lu wenyi,1,2 Chen Yuting,1,2 Jianlin Qiao,1– 3 Kailin Xu,1– 3 Lingyu Zeng1– 3 1Department of Blood Diseases Institute, Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of China; 2Department of Key Laboratory of the Bone Marrow Stem Cell, Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of ChinaCorrespondence: Kailin Xu; Lingyu Zeng Tel +8615162166166; +8613685182368Email lihmd@163.com; zengly2000@163.comIntroduction: The extend to the clinical benefit of radiation therapy is the inability to eliminate only cancer cells and destroy normal cells such as microvascular endothelial in the vascular niche and turn induced-inflammasome signaling and cell death. These unfortunate injuries generated by ionizing radiation alter the therapeutic window and result in the re-occurrence of the malignancy. Therefore, we engaged in vitro studies by demonstrating radiation-induced inflammasome and cell death in endothelial cells.Methods: The microvascular endothelial cells were cultured in a sterile dish, then kept in a humidifier of 5% at 37°C for 12 hours/more to attain confluence, and exposed at a dose of 1.8Gy/min achieve the coveted amounts except for the control. The cells were harvested 24 hours post-irradiation.Results: Our findings indicate that gamma radiation activates the NOD-like receptor (NLR) family of NLRP1 and NLRP3 complex in microvascular endothelial cells. These complexes activate the inactive precursor of caspase-1, which cleaved to bioactive caspase − 1 and enhances the production of pro-inflammatory cytokines of interleukin-1β and interleukin-18 that induce the dependent pyroptotic, which results in the production of chemokines, tumor necrosis factor-alpha (TNF-α), and high-mobility group protein-1 (HMGB-1). We also discovered the radiation could directly prompt caspase − 1, which auto-cleaved to activate gasdermin D to potentiate pyroptosis independently.Discussion: Overall, these findings suggested that reducing the unfavorable effect of radiation injuries could be challenging since gamma radiation induces the microvascular endothelial cells to cell death and activates the inflammasome signaling via different pathways.Keywords: gamma radiation, microvascular endothelial cells, ECs, NOD-like receptor, NLR, inflammasome, pyroptosisSmith AOJu WAdzraku SYwenyi LYuting CQiao JXu KZeng LDove Medical Pressarticlegamma radiationmicrovascular endothelial cells (ecs)nod-like receptor (nlr)inflammasomeand pyroptosis.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3277-3288 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gamma radiation microvascular endothelial cells (ecs) nod-like receptor (nlr) inflammasome and pyroptosis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	gamma radiation microvascular endothelial cells (ecs) nod-like receptor (nlr) inflammasome and pyroptosis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Smith AO Ju W Adzraku SY wenyi L Yuting C Qiao J Xu K Zeng L Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
description	Alhaji Osman Smith,1,2 Wen Ju,1– 3 Seyram Yao Adzraku,1,2 Lu wenyi,1,2 Chen Yuting,1,2 Jianlin Qiao,1– 3 Kailin Xu,1– 3 Lingyu Zeng1– 3 1Department of Blood Diseases Institute, Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of China; 2Department of Key Laboratory of the Bone Marrow Stem Cell, Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, 221002, Jiangsu Province, People’s Republic of ChinaCorrespondence: Kailin Xu; Lingyu Zeng Tel +8615162166166; +8613685182368Email lihmd@163.com; zengly2000@163.comIntroduction: The extend to the clinical benefit of radiation therapy is the inability to eliminate only cancer cells and destroy normal cells such as microvascular endothelial in the vascular niche and turn induced-inflammasome signaling and cell death. These unfortunate injuries generated by ionizing radiation alter the therapeutic window and result in the re-occurrence of the malignancy. Therefore, we engaged in vitro studies by demonstrating radiation-induced inflammasome and cell death in endothelial cells.Methods: The microvascular endothelial cells were cultured in a sterile dish, then kept in a humidifier of 5% at 37°C for 12 hours/more to attain confluence, and exposed at a dose of 1.8Gy/min achieve the coveted amounts except for the control. The cells were harvested 24 hours post-irradiation.Results: Our findings indicate that gamma radiation activates the NOD-like receptor (NLR) family of NLRP1 and NLRP3 complex in microvascular endothelial cells. These complexes activate the inactive precursor of caspase-1, which cleaved to bioactive caspase − 1 and enhances the production of pro-inflammatory cytokines of interleukin-1β and interleukin-18 that induce the dependent pyroptotic, which results in the production of chemokines, tumor necrosis factor-alpha (TNF-α), and high-mobility group protein-1 (HMGB-1). We also discovered the radiation could directly prompt caspase − 1, which auto-cleaved to activate gasdermin D to potentiate pyroptosis independently.Discussion: Overall, these findings suggested that reducing the unfavorable effect of radiation injuries could be challenging since gamma radiation induces the microvascular endothelial cells to cell death and activates the inflammasome signaling via different pathways.Keywords: gamma radiation, microvascular endothelial cells, ECs, NOD-like receptor, NLR, inflammasome, pyroptosis
format	article
author	Smith AO Ju W Adzraku SY wenyi L Yuting C Qiao J Xu K Zeng L
author_facet	Smith AO Ju W Adzraku SY wenyi L Yuting C Qiao J Xu K Zeng L
author_sort	Smith AO
title	Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
title_short	Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
title_full	Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
title_fullStr	Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
title_full_unstemmed	Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells
title_sort	gamma radiation induce inflammasome signaling and pyroptosis in microvascular endothelial cells
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/d890e705fcea4b6287e5a361d8ed0684
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Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells

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