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
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/14248

id RIUCA_63793327e61146418201e7b0da41c7e7
oai_identifier_str oai:ucacris:123456789/14248
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
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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