Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway
- Autores
- Zhang, Ye; Yang, Xue; Yan, Wenchao; Li, Rui; Ye, Qian; You, Linjun; Xie, Wenhao; Mo, Kun; Fu, Ruifeng; Wang, Yanxiang; Chen, Yufei; Hou, Hui; Yang, Yong; Birnbaumer, Lutz; Di, Qin; Li, Xianjing
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fil: Zhang, Ye. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Yang, Xue. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Yan, Wenchao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Li, Rui. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Ye, Qian. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: You, Linjun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Xie, Wenhao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Mo, Kun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Fu, Ruifeng. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Yanxiang. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Chen, Yufei. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Di, Qin. Nanjing Sport Institute. School of Sports and Health; China
Fil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China
Abstract: Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Δ12,14 -prostaglandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders. - Fuente
- FASEB Journal. 2020, 34(9)
- Materia
-
CITOQUINAS
INFLAMACION
SEPSIS
TIMOPENTINA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/14248
Ver los metadatos del registro completo
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oai:ucacris:123456789/14248 |
network_acronym_str |
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repository_id_str |
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network_name_str |
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spelling |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathwayZhang, YeYang, XueYan, WenchaoLi, RuiYe, QianYou, LinjunXie, WenhaoMo, KunFu, RuifengWang, YanxiangChen, YufeiHou, HuiYang, YongBirnbaumer, LutzDi, QinLi, XianjingCITOQUINASINFLAMACIONSEPSISTIMOPENTINAFil: Zhang, Ye. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Yang, Xue. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Yan, Wenchao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Li, Rui. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Ye, Qian. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: You, Linjun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Xie, Wenhao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Mo, Kun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Fu, Ruifeng. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Yanxiang. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Chen, Yufei. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di, Qin. Nanjing Sport Institute. School of Sports and Health; ChinaFil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; ChinaAbstract: Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Δ12,14 -prostaglandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders.WileyFederation of American Society of Experimental Biology (FASEB)2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/142480892-66381530-6860 (online)10.1096/fj.202000467R32652815Zhang, Y., et al. Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway [en línea]. FASEB Journal. 2020, 34(9) doi:10.1096/fj.202000467R Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14248FASEB Journal. 2020, 34(9)reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:58:38Zoai:ucacris:123456789/14248instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:58:38.397Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse |
dc.title.none.fl_str_mv |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
title |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
spellingShingle |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway Zhang, Ye CITOQUINAS INFLAMACION SEPSIS TIMOPENTINA |
title_short |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
title_full |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
title_fullStr |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
title_full_unstemmed |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
title_sort |
Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway |
dc.creator.none.fl_str_mv |
Zhang, Ye Yang, Xue Yan, Wenchao Li, Rui Ye, Qian You, Linjun Xie, Wenhao Mo, Kun Fu, Ruifeng Wang, Yanxiang Chen, Yufei Hou, Hui Yang, Yong Birnbaumer, Lutz Di, Qin Li, Xianjing |
author |
Zhang, Ye |
author_facet |
Zhang, Ye Yang, Xue Yan, Wenchao Li, Rui Ye, Qian You, Linjun Xie, Wenhao Mo, Kun Fu, Ruifeng Wang, Yanxiang Chen, Yufei Hou, Hui Yang, Yong Birnbaumer, Lutz Di, Qin Li, Xianjing |
author_role |
author |
author2 |
Yang, Xue Yan, Wenchao Li, Rui Ye, Qian You, Linjun Xie, Wenhao Mo, Kun Fu, Ruifeng Wang, Yanxiang Chen, Yufei Hou, Hui Yang, Yong Birnbaumer, Lutz Di, Qin Li, Xianjing |
author2_role |
author author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
CITOQUINAS INFLAMACION SEPSIS TIMOPENTINA |
topic |
CITOQUINAS INFLAMACION SEPSIS TIMOPENTINA |
dc.description.none.fl_txt_mv |
Fil: Zhang, Ye. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Yang, Xue. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Yan, Wenchao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Li, Rui. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Ye, Qian. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: You, Linjun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Xie, Wenhao. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Mo, Kun. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Fu, Ruifeng. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Wang, Yanxiang. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Chen, Yufei. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Yang, Yong. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Di, Qin. Nanjing Sport Institute. School of Sports and Health; China Fil: Li, Xianjing. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China Abstract: Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Δ12,14 -prostaglandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders. |
description |
Fil: Zhang, Ye. China Pharmaceutical University. State Key Laboratory of Natural Medicines. Center for New Drug Safety Evaluation and Research; China |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
https://repositorio.uca.edu.ar/handle/123456789/14248 0892-6638 1530-6860 (online) 10.1096/fj.202000467R 32652815 Zhang, Y., et al. Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway [en línea]. FASEB Journal. 2020, 34(9) doi:10.1096/fj.202000467R Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14248 |
url |
https://repositorio.uca.edu.ar/handle/123456789/14248 |
identifier_str_mv |
0892-6638 1530-6860 (online) 10.1096/fj.202000467R 32652815 Zhang, Y., et al. Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway [en línea]. FASEB Journal. 2020, 34(9) doi:10.1096/fj.202000467R Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14248 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Federation of American Society of Experimental Biology (FASEB) |
publisher.none.fl_str_mv |
Wiley Federation of American Society of Experimental Biology (FASEB) |
dc.source.none.fl_str_mv |
FASEB Journal. 2020, 34(9) reponame:Repositorio Institucional (UCA) instname:Pontificia Universidad Católica Argentina |
reponame_str |
Repositorio Institucional (UCA) |
collection |
Repositorio Institucional (UCA) |
instname_str |
Pontificia Universidad Católica Argentina |
repository.name.fl_str_mv |
Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina |
repository.mail.fl_str_mv |
claudia_fernandez@uca.edu.ar |
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1836638362595753984 |
score |
13.13397 |