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dc.contributor.author
Zhou, Xikun
dc.contributor.author
Ye, Yan
dc.contributor.author
Sun, Yuyang
dc.contributor.author
Li, Xuefeng
dc.contributor.author
Wang, Wenxue
dc.contributor.author
Privratsky, Breanna
dc.contributor.author
Tan, Shirui
dc.contributor.author
Zhou, Zongguang
dc.contributor.author
Huang, Canhua
dc.contributor.author
Wei, Yu-Quan
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Singh, Brij B.
dc.contributor.author
Wu, Min
dc.date.available
2018-03-20T18:12:10Z
dc.date.issued
2015-08
dc.identifier.citation
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
dc.identifier.issn
0270-7306
dc.identifier.uri
http://hdl.handle.net/11336/39387
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trpc1
dc.subject
Tlr4
dc.subject
Host Defence
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-02T17:33:03Z
dc.journal.volume
35
dc.journal.number
16
dc.journal.pagination
2729-2739
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Zhou, Xikun. University Of North Dakota; Estados Unidos. West China Hospital Of Sichuan University; China
dc.description.fil
Fil: Ye, Yan. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Sun, Yuyang. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Li, Xuefeng. West China Hospital Of Sichuan University; China. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Wang, Wenxue. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Privratsky, Breanna. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Tan, Shirui. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Zhou, Zongguang. West China Hospital Of Sichuan University; China
dc.description.fil
Fil: Huang, Canhua. West China Hospital Of Sichuan University; China
dc.description.fil
Fil: Wei, Yu-Quan. West China Hospital Of Sichuan University; China
dc.description.fil
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute Of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Singh, Brij B.. University Of North Dakota; Estados Unidos
dc.description.fil
Fil: Wu, Min. University Of North Dakota; Estados Unidos
dc.journal.title
Molecular and Cellular Biology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/MCB.00256-15
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://mcb.asm.org/content/35/16/2729
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