Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling

Autores
Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; Privratsky, Breanna; Tan, Shirui; Zhou, Zongguang; Huang, Canhua; Wei, Yu-Quan; Birnbaumer, Lutz; Singh, Brij B.; Wu, Min
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca2+ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1-/- mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca2+ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca2+ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca2+ entry and triggered protein kinase Cα (PKC-α) activity to facilitate nuclear translocation of NF-kB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCγ signaling circuit.
Fil: Zhou, Xikun. University Of North Dakota; Estados Unidos. West China Hospital Of Sichuan University; China
Fil: Ye, Yan. University Of North Dakota; Estados Unidos
Fil: Sun, Yuyang. University Of North Dakota; Estados Unidos
Fil: Li, Xuefeng. West China Hospital Of Sichuan University; China. University Of North Dakota; Estados Unidos
Fil: Wang, Wenxue. University Of North Dakota; Estados Unidos
Fil: Privratsky, Breanna. University Of North Dakota; Estados Unidos
Fil: Tan, Shirui. University Of North Dakota; Estados Unidos
Fil: Zhou, Zongguang. West China Hospital Of Sichuan University; China
Fil: Huang, Canhua. West China Hospital Of Sichuan University; China
Fil: Wei, Yu-Quan. West China Hospital Of Sichuan University; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Singh, Brij B.. University Of North Dakota; Estados Unidos
Fil: Wu, Min. University Of North Dakota; Estados Unidos
Materia
TRPC1
TLR4
host defence
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:11336/39387
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/39387
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signalingZhou, XikunYe, YanSun, YuyangLi, XuefengWang, WenxuePrivratsky, BreannaTan, ShiruiZhou, ZongguangHuang, CanhuaWei, Yu-QuanBirnbaumer, LutzSingh, Brij B.Wu, MinTRPC1TLR4host defencehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca2+ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1-/- mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca2+ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca2+ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca2+ entry and triggered protein kinase Cα (PKC-α) activity to facilitate nuclear translocation of NF-kB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCγ signaling circuit.Fil: Zhou, Xikun. University Of North Dakota; Estados Unidos. West China Hospital Of Sichuan University; ChinaFil: Ye, Yan. University Of North Dakota; Estados UnidosFil: Sun, Yuyang. University Of North Dakota; Estados UnidosFil: Li, Xuefeng. West China Hospital Of Sichuan University; China. University Of North Dakota; Estados UnidosFil: Wang, Wenxue. University Of North Dakota; Estados UnidosFil: Privratsky, Breanna. University Of North Dakota; Estados UnidosFil: Tan, Shirui. University Of North Dakota; Estados UnidosFil: Zhou, Zongguang. West China Hospital Of Sichuan University; ChinaFil: Huang, Canhua. West China Hospital Of Sichuan University; ChinaFil: Wei, Yu-Quan. West China Hospital Of Sichuan University; ChinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute Of Environmental Health Sciences; Estados UnidosFil: Singh, Brij B.. University Of North Dakota; Estados UnidosFil: Wu, Min. University Of North Dakota; Estados UnidosAmerican Society for Microbiology2015-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39387Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; et al.; Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling; American Society for Microbiology; Molecular and Cellular Biology; 35; 16; 8-2015; 2729-27390270-7306CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/MCB.00256-15info:eu-repo/semantics/altIdentifier/url/http://mcb.asm.org/content/35/16/2729info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:54:02Zoai:ri.conicet.gov.ar:11336/39387instacron: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:34982026-08-25 14:54:03.008CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
title Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
spellingShingle Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
Zhou, Xikun
TRPC1
TLR4
host defence
title_short Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
title_full Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
title_fullStr Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
title_full_unstemmed Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
title_sort Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
dc.creator.none.fl_str_mv Zhou, Xikun
Ye, Yan
Sun, Yuyang
Li, Xuefeng
Wang, Wenxue
Privratsky, Breanna
Tan, Shirui
Zhou, Zongguang
Huang, Canhua
Wei, Yu-Quan
Birnbaumer, Lutz
Singh, Brij B.
Wu, Min
author Zhou, Xikun
author_facet Zhou, Xikun
Ye, Yan
Sun, Yuyang
Li, Xuefeng
Wang, Wenxue
Privratsky, Breanna
Tan, Shirui
Zhou, Zongguang
Huang, Canhua
Wei, Yu-Quan
Birnbaumer, Lutz
Singh, Brij B.
Wu, Min
author_role author
author2 Ye, Yan
Sun, Yuyang
Li, Xuefeng
Wang, Wenxue
Privratsky, Breanna
Tan, Shirui
Zhou, Zongguang
Huang, Canhua
Wei, Yu-Quan
Birnbaumer, Lutz
Singh, Brij B.
Wu, Min
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC1
TLR4
host defence
topic TRPC1
TLR4
host defence
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca2+ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1-/- mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca2+ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca2+ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca2+ entry and triggered protein kinase Cα (PKC-α) activity to facilitate nuclear translocation of NF-kB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCγ signaling circuit.
Fil: Zhou, Xikun. University Of North Dakota; Estados Unidos. West China Hospital Of Sichuan University; China
Fil: Ye, Yan. University Of North Dakota; Estados Unidos
Fil: Sun, Yuyang. University Of North Dakota; Estados Unidos
Fil: Li, Xuefeng. West China Hospital Of Sichuan University; China. University Of North Dakota; Estados Unidos
Fil: Wang, Wenxue. University Of North Dakota; Estados Unidos
Fil: Privratsky, Breanna. University Of North Dakota; Estados Unidos
Fil: Tan, Shirui. University Of North Dakota; Estados Unidos
Fil: Zhou, Zongguang. West China Hospital Of Sichuan University; China
Fil: Huang, Canhua. West China Hospital Of Sichuan University; China
Fil: Wei, Yu-Quan. West China Hospital Of Sichuan University; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute Of Environmental Health Sciences; Estados Unidos
Fil: Singh, Brij B.. University Of North Dakota; Estados Unidos
Fil: Wu, Min. University Of North Dakota; Estados Unidos
description Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca2+ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1-/- mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca2+ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca2+ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca2+ entry and triggered protein kinase Cα (PKC-α) activity to facilitate nuclear translocation of NF-kB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCγ signaling circuit.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
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/11336/39387
Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; et al.; Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling; American Society for Microbiology; Molecular and Cellular Biology; 35; 16; 8-2015; 2729-2739
0270-7306
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39387
identifier_str_mv Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; et al.; Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling; American Society for Microbiology; Molecular and Cellular Biology; 35; 16; 8-2015; 2729-2739
0270-7306
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/MCB.00256-15
info:eu-repo/semantics/altIdentifier/url/http://mcb.asm.org/content/35/16/2729
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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
_version_ 1874774851547299840
score 13.365483

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