Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1

Autores
Li, Xiaolin; Wang, Duowei; Chen, Zen; Lu, Ermei; Wang, Zhuo; Duan, Jingjing; Tian, Wei; Wang, Yun; You, Linjun; Zou, Yulian; Cheng, Yan; Zhu, Qingyi; Wan, Xiaojian; Xia, Tao; Birnbaumer, Lutz; Yang, Yong
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.
Fil: Li, Xiaolin. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Duowei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Chen, Zen. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lu, Ermei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Zhuo. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Duan, Jingjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Tian, Wei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Yun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: You, Linjun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zou, Yulian. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Cheng, Yan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhu, Qingyi. Jiangsu Province Hospital of Traditional Chinese Medicine. Departament of Urology; China
Fil: Wan, Xiaojian. Second Military Medical University. Department of Anesthesiology and Intensive Care Medicine, Changhai Hospita; China
Fil: Xia, Tao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology, ; Estados Unidos
Fil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Materia
ENDOSOME
GΑI1
GΑI3
MACROPHAGE POLARIZATION
TOLL-LIKE RECEPTOR 4
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:11336/93463
Acceder
id CONICETDig_03ddc55b4511a2e56db77c10dee03e3e
oai_identifier_str oai:ri.conicet.gov.ar:11336/93463
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1Li, XiaolinWang, DuoweiChen, ZenLu, ErmeiWang, ZhuoDuan, JingjingTian, WeiWang, YunYou, LinjunZou, YulianCheng, YanZhu, QingyiWan, XiaojianXia, TaoBirnbaumer, LutzYang, YongENDOSOMEGΑI1GΑI3MACROPHAGE POLARIZATIONTOLL-LIKE RECEPTOR 4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.Fil: Li, Xiaolin. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Duowei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Chen, Zen. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Lu, Ermei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Zhuo. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Duan, Jingjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Tian, Wei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Yun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: You, Linjun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zou, Yulian. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Cheng, Yan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zhu, Qingyi. Jiangsu Province Hospital of Traditional Chinese Medicine. Departament of Urology; ChinaFil: Wan, Xiaojian. Second Military Medical University. Department of Anesthesiology and Intensive Care Medicine, Changhai Hospita; ChinaFil: Xia, Tao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology, ; Estados UnidosFil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaNational Academy of Sciences2015-04-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/93463Li, Xiaolin; Wang, Duowei; Chen, Zen; Lu, Ermei; Wang, Zhuo; et al.; Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 15; 14-4-2015; 4731-47360027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/112/15/4731info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403188/info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1503779112info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T14:41:05Zoai:ri.conicet.gov.ar:11336/93463instacron: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:34982025-12-23 14:41:05.803CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
title Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
spellingShingle Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
Li, Xiaolin
ENDOSOME
GΑI1
GΑI3
MACROPHAGE POLARIZATION
TOLL-LIKE RECEPTOR 4
title_short Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
title_full Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
title_fullStr Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
title_full_unstemmed Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
title_sort Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1
dc.creator.none.fl_str_mv Li, Xiaolin
Wang, Duowei
Chen, Zen
Lu, Ermei
Wang, Zhuo
Duan, Jingjing
Tian, Wei
Wang, Yun
You, Linjun
Zou, Yulian
Cheng, Yan
Zhu, Qingyi
Wan, Xiaojian
Xia, Tao
Birnbaumer, Lutz
Yang, Yong
author Li, Xiaolin
author_facet Li, Xiaolin
Wang, Duowei
Chen, Zen
Lu, Ermei
Wang, Zhuo
Duan, Jingjing
Tian, Wei
Wang, Yun
You, Linjun
Zou, Yulian
Cheng, Yan
Zhu, Qingyi
Wan, Xiaojian
Xia, Tao
Birnbaumer, Lutz
Yang, Yong
author_role author
author2 Wang, Duowei
Chen, Zen
Lu, Ermei
Wang, Zhuo
Duan, Jingjing
Tian, Wei
Wang, Yun
You, Linjun
Zou, Yulian
Cheng, Yan
Zhu, Qingyi
Wan, Xiaojian
Xia, Tao
Birnbaumer, Lutz
Yang, Yong
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENDOSOME
GΑI1
GΑI3
MACROPHAGE POLARIZATION
TOLL-LIKE RECEPTOR 4
topic ENDOSOME
GΑI1
GΑI3
MACROPHAGE POLARIZATION
TOLL-LIKE RECEPTOR 4
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.
Fil: Li, Xiaolin. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Duowei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Chen, Zen. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Lu, Ermei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Zhuo. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Duan, Jingjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Tian, Wei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Wang, Yun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: You, Linjun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zou, Yulian. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Cheng, Yan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Zhu, Qingyi. Jiangsu Province Hospital of Traditional Chinese Medicine. Departament of Urology; China
Fil: Wan, Xiaojian. Second Military Medical University. Department of Anesthesiology and Intensive Care Medicine, Changhai Hospita; China
Fil: Xia, Tao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology, ; Estados Unidos
Fil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; China
description Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.
publishDate 2015
dc.date.none.fl_str_mv 2015-04-14
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/11336/93463
Li, Xiaolin; Wang, Duowei; Chen, Zen; Lu, Ermei; Wang, Zhuo; et al.; Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 15; 14-4-2015; 4731-4736
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/93463
identifier_str_mv Li, Xiaolin; Wang, Duowei; Chen, Zen; Lu, Ermei; Wang, Zhuo; et al.; Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 15; 14-4-2015; 4731-4736
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/112/15/4731
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403188/
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1503779112
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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 13.049097

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