Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response
Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1β and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis an...
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doaj-dbf9a3b759374c8a8a98cb0e110f15e92020-11-25T03:42:32ZengHindawi LimitedBioMed Research International2314-61332314-61412020-01-01202010.1155/2020/59603755960375Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic ResponseLuo Zhuo0Xiaobing Chen1Yan Sun2Yanli Wang3Yuanfeng Shi4Lin Bu5Wei Xia6Jiayan Han7Dongmei Chen8Xiaomin Li9Department of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Clinical Medical School of Nanjing Medical University Affiliated Hospital of Lianyungang First People’s Hospital, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Critical Care Medicine, Xuzhou Medical University Affiliated Hospital, No. 99 West Huaihai Road, Xuzhou 221000, ChinaDepartment of Intensive Care Unit, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi 214000, ChinaDepartment of Emergency Medicine, The Clinical Medical School of Nanjing Medical University Affiliated Hospital of Lianyungang First People’s Hospital, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaDepartment of Emergency Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 North Tongguan Road, Lianyungang 222002, ChinaPyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1β and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1β, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1β and IL-18 by inhibiting pyroptosis and enhancing autophagy.http://dx.doi.org/10.1155/2020/5960375 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luo Zhuo Xiaobing Chen Yan Sun Yanli Wang Yuanfeng Shi Lin Bu Wei Xia Jiayan Han Dongmei Chen Xiaomin Li |
spellingShingle |
Luo Zhuo Xiaobing Chen Yan Sun Yanli Wang Yuanfeng Shi Lin Bu Wei Xia Jiayan Han Dongmei Chen Xiaomin Li Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response BioMed Research International |
author_facet |
Luo Zhuo Xiaobing Chen Yan Sun Yanli Wang Yuanfeng Shi Lin Bu Wei Xia Jiayan Han Dongmei Chen Xiaomin Li |
author_sort |
Luo Zhuo |
title |
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response |
title_short |
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response |
title_full |
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response |
title_fullStr |
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response |
title_full_unstemmed |
Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response |
title_sort |
rapamycin inhibited pyroptosis and reduced the release of il-1β and il-18 in the septic response |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2020-01-01 |
description |
Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1β and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1β, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1β and IL-18 by inhibiting pyroptosis and enhancing autophagy. |
url |
http://dx.doi.org/10.1155/2020/5960375 |
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