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
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.
Fil: Zhang, Ye. China Pharmaceutical University; China
Fil: Yang, Xue. China Pharmaceutical University; China
Fil: Yan, Wenchao. China Pharmaceutical University; China
Fil: Li, Rui. China Pharmaceutical University; China
Fil: Ye, Qian. China Pharmaceutical University; China
Fil: You, Linjun. China Pharmaceutical University; China
Fil: Xie, Wenhao. China Pharmaceutical University; China
Fil: Mo, Kun. China Pharmaceutical University; China
Fil: Fu, Ruifeng. China Pharmaceutical University; China
Fil: Wang, Yanxiang. China Pharmaceutical University; China
Fil: Chen, Yufei. China Pharmaceutical University; China
Fil: Hou, Hui. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Di, Qin. Nanjing Sport Institute; China
Fil: Li, Xianjing. China Pharmaceutical University; China
Materia
15-D-PGJ2
MACROPHAGE
PPARΓ
SEPSIS
THYMOPENTIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/140666
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/140666
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
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, Xianjing15-D-PGJ2MACROPHAGEPPARΓSEPSISTHYMOPENTINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Sepsis, 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.Fil: Zhang, Ye. China Pharmaceutical University; ChinaFil: Yang, Xue. China Pharmaceutical University; ChinaFil: Yan, Wenchao. China Pharmaceutical University; ChinaFil: Li, Rui. China Pharmaceutical University; ChinaFil: Ye, Qian. China Pharmaceutical University; ChinaFil: You, Linjun. China Pharmaceutical University; ChinaFil: Xie, Wenhao. China Pharmaceutical University; ChinaFil: Mo, Kun. China Pharmaceutical University; ChinaFil: Fu, Ruifeng. China Pharmaceutical University; ChinaFil: Wang, Yanxiang. China Pharmaceutical University; ChinaFil: Chen, Yufei. China Pharmaceutical University; ChinaFil: Hou, Hui. China Pharmaceutical University; ChinaFil: Yang, Yong. China Pharmaceutical University; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Di, Qin. Nanjing Sport Institute; ChinaFil: Li, Xianjing. China Pharmaceutical University; ChinaFederation of American Societies for Experimental Biology2020-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140666Zhang, Ye; Yang, Xue; Yan, Wenchao; Li, Rui; Ye, Qian; et al.; Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway; Federation of American Societies for Experimental Biology; FASEB Journal; 34; 9; 9-2020; 11772-117850892-6638CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.202000467Rinfo:eu-repo/semantics/altIdentifier/url/https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202000467Rinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:25Zoai:ri.conicet.gov.ar:11336/140666instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:05:26.193CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
15-D-PGJ2
MACROPHAGE
PPARΓ
SEPSIS
THYMOPENTIN
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 15-D-PGJ2
MACROPHAGE
PPARΓ
SEPSIS
THYMOPENTIN
topic 15-D-PGJ2
MACROPHAGE
PPARΓ
SEPSIS
THYMOPENTIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Zhang, Ye. China Pharmaceutical University; China
Fil: Yang, Xue. China Pharmaceutical University; China
Fil: Yan, Wenchao. China Pharmaceutical University; China
Fil: Li, Rui. China Pharmaceutical University; China
Fil: Ye, Qian. China Pharmaceutical University; China
Fil: You, Linjun. China Pharmaceutical University; China
Fil: Xie, Wenhao. China Pharmaceutical University; China
Fil: Mo, Kun. China Pharmaceutical University; China
Fil: Fu, Ruifeng. China Pharmaceutical University; China
Fil: Wang, Yanxiang. China Pharmaceutical University; China
Fil: Chen, Yufei. China Pharmaceutical University; China
Fil: Hou, Hui. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Di, Qin. Nanjing Sport Institute; China
Fil: Li, Xianjing. China Pharmaceutical University; China
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
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 http://hdl.handle.net/11336/140666
Zhang, Ye; Yang, Xue; Yan, Wenchao; Li, Rui; Ye, Qian; et al.; Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway; Federation of American Societies for Experimental Biology; FASEB Journal; 34; 9; 9-2020; 11772-11785
0892-6638
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140666
identifier_str_mv Zhang, Ye; Yang, Xue; Yan, Wenchao; Li, Rui; Ye, Qian; et al.; Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway; Federation of American Societies for Experimental Biology; FASEB Journal; 34; 9; 9-2020; 11772-11785
0892-6638
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.202000467R
info:eu-repo/semantics/altIdentifier/url/https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202000467R
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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