SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells

Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein...
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Autor*in:	Villacampa, Alicia [verfasserIn] Alfaro, Enrique Morales, Cristina Díaz-García, Elena López-Fernández, Cristina Bartha, José Luis López-Sánchez, Francisco Lorenzo, Óscar Moncada, Salvador Sánchez-Ferrer, Carlos F. García-Río, Francisco Cubillos-Zapata, Carolina Peiró, Concepción

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Blood coagulation factors SARS-CoV-2 Endothelial cells NLRP3 inflammasome Monocytes

Anmerkung:	© The Author(s) 2024. corrected publication 2024

Übergeordnetes Werk:	Enthalten in: Cell communication and signaling - London : Biomed Central, 2003, 22(2024), 1 vom: 15. Jan.
Übergeordnetes Werk:	volume:22 ; year:2024 ; number:1 ; day:15 ; month:01

Links:	Volltext

DOI / URN:	10.1186/s12964-023-01397-6

Katalog-ID:	SPR054397855

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520			\|a Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract
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allfields	10.1186/s12964-023-01397-6 doi (DE-627)SPR054397855 (SPR)s12964-023-01397-6-e DE-627 ger DE-627 rakwb eng Villacampa, Alicia verfasserin aut SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024. corrected publication 2024 Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213 Alfaro, Enrique aut Morales, Cristina aut Díaz-García, Elena aut López-Fernández, Cristina aut Bartha, José Luis aut López-Sánchez, Francisco aut Lorenzo, Óscar aut Moncada, Salvador aut Sánchez-Ferrer, Carlos F. aut García-Río, Francisco aut Cubillos-Zapata, Carolina aut Peiró, Concepción aut Enthalten in Cell communication and signaling London : Biomed Central, 2003 22(2024), 1 vom: 15. Jan. (DE-627)37375275X (DE-600)2126315-2 1478-811X nnns volume:22 year:2024 number:1 day:15 month:01 https://dx.doi.org/10.1186/s12964-023-01397-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 15 01
spelling	10.1186/s12964-023-01397-6 doi (DE-627)SPR054397855 (SPR)s12964-023-01397-6-e DE-627 ger DE-627 rakwb eng Villacampa, Alicia verfasserin aut SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024. corrected publication 2024 Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213 Alfaro, Enrique aut Morales, Cristina aut Díaz-García, Elena aut López-Fernández, Cristina aut Bartha, José Luis aut López-Sánchez, Francisco aut Lorenzo, Óscar aut Moncada, Salvador aut Sánchez-Ferrer, Carlos F. aut García-Río, Francisco aut Cubillos-Zapata, Carolina aut Peiró, Concepción aut Enthalten in Cell communication and signaling London : Biomed Central, 2003 22(2024), 1 vom: 15. Jan. (DE-627)37375275X (DE-600)2126315-2 1478-811X nnns volume:22 year:2024 number:1 day:15 month:01 https://dx.doi.org/10.1186/s12964-023-01397-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 15 01
allfields_unstemmed	10.1186/s12964-023-01397-6 doi (DE-627)SPR054397855 (SPR)s12964-023-01397-6-e DE-627 ger DE-627 rakwb eng Villacampa, Alicia verfasserin aut SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024. corrected publication 2024 Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213 Alfaro, Enrique aut Morales, Cristina aut Díaz-García, Elena aut López-Fernández, Cristina aut Bartha, José Luis aut López-Sánchez, Francisco aut Lorenzo, Óscar aut Moncada, Salvador aut Sánchez-Ferrer, Carlos F. aut García-Río, Francisco aut Cubillos-Zapata, Carolina aut Peiró, Concepción aut Enthalten in Cell communication and signaling London : Biomed Central, 2003 22(2024), 1 vom: 15. Jan. (DE-627)37375275X (DE-600)2126315-2 1478-811X nnns volume:22 year:2024 number:1 day:15 month:01 https://dx.doi.org/10.1186/s12964-023-01397-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 15 01
allfieldsGer	10.1186/s12964-023-01397-6 doi (DE-627)SPR054397855 (SPR)s12964-023-01397-6-e DE-627 ger DE-627 rakwb eng Villacampa, Alicia verfasserin aut SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024. corrected publication 2024 Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213 Alfaro, Enrique aut Morales, Cristina aut Díaz-García, Elena aut López-Fernández, Cristina aut Bartha, José Luis aut López-Sánchez, Francisco aut Lorenzo, Óscar aut Moncada, Salvador aut Sánchez-Ferrer, Carlos F. aut García-Río, Francisco aut Cubillos-Zapata, Carolina aut Peiró, Concepción aut Enthalten in Cell communication and signaling London : Biomed Central, 2003 22(2024), 1 vom: 15. Jan. (DE-627)37375275X (DE-600)2126315-2 1478-811X nnns volume:22 year:2024 number:1 day:15 month:01 https://dx.doi.org/10.1186/s12964-023-01397-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 15 01
allfieldsSound	10.1186/s12964-023-01397-6 doi (DE-627)SPR054397855 (SPR)s12964-023-01397-6-e DE-627 ger DE-627 rakwb eng Villacampa, Alicia verfasserin aut SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024. corrected publication 2024 Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213 Alfaro, Enrique aut Morales, Cristina aut Díaz-García, Elena aut López-Fernández, Cristina aut Bartha, José Luis aut López-Sánchez, Francisco aut Lorenzo, Óscar aut Moncada, Salvador aut Sánchez-Ferrer, Carlos F. aut García-Río, Francisco aut Cubillos-Zapata, Carolina aut Peiró, Concepción aut Enthalten in Cell communication and signaling London : Biomed Central, 2003 22(2024), 1 vom: 15. Jan. (DE-627)37375275X (DE-600)2126315-2 1478-811X nnns volume:22 year:2024 number:1 day:15 month:01 https://dx.doi.org/10.1186/s12964-023-01397-6 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 15 01
language	English
source	Enthalten in Cell communication and signaling 22(2024), 1 vom: 15. Jan. volume:22 year:2024 number:1 day:15 month:01
sourceStr	Enthalten in Cell communication and signaling 22(2024), 1 vom: 15. Jan. volume:22 year:2024 number:1 day:15 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Blood coagulation factors SARS-CoV-2 Endothelial cells NLRP3 inflammasome Monocytes
isfreeaccess_bool	true
container_title	Cell communication and signaling
authorswithroles_txt_mv	Villacampa, Alicia @@aut@@ Alfaro, Enrique @@aut@@ Morales, Cristina @@aut@@ Díaz-García, Elena @@aut@@ López-Fernández, Cristina @@aut@@ Bartha, José Luis @@aut@@ López-Sánchez, Francisco @@aut@@ Lorenzo, Óscar @@aut@@ Moncada, Salvador @@aut@@ Sánchez-Ferrer, Carlos F. @@aut@@ García-Río, Francisco @@aut@@ Cubillos-Zapata, Carolina @@aut@@ Peiró, Concepción @@aut@@
publishDateDaySort_date	2024-01-15T00:00:00Z
hierarchy_top_id	37375275X
id	SPR054397855
language_de	englisch
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The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. 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author	Villacampa, Alicia
spellingShingle	Villacampa, Alicia misc Blood coagulation factors misc SARS-CoV-2 misc Endothelial cells misc NLRP3 inflammasome misc Monocytes SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
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topic_title	SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells Blood coagulation factors (dpeaa)DE-He213 SARS-CoV-2 (dpeaa)DE-He213 Endothelial cells (dpeaa)DE-He213 NLRP3 inflammasome (dpeaa)DE-He213 Monocytes (dpeaa)DE-He213
topic	misc Blood coagulation factors misc SARS-CoV-2 misc Endothelial cells misc NLRP3 inflammasome misc Monocytes
topic_unstemmed	misc Blood coagulation factors misc SARS-CoV-2 misc Endothelial cells misc NLRP3 inflammasome misc Monocytes
topic_browse	misc Blood coagulation factors misc SARS-CoV-2 misc Endothelial cells misc NLRP3 inflammasome misc Monocytes
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title	SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
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title_full	SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
author_sort	Villacampa, Alicia
journal	Cell communication and signaling
journalStr	Cell communication and signaling
lang_code	eng
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author_browse	Villacampa, Alicia Alfaro, Enrique Morales, Cristina Díaz-García, Elena López-Fernández, Cristina Bartha, José Luis López-Sánchez, Francisco Lorenzo, Óscar Moncada, Salvador Sánchez-Ferrer, Carlos F. García-Río, Francisco Cubillos-Zapata, Carolina Peiró, Concepción
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format_se	Elektronische Aufsätze
author-letter	Villacampa, Alicia
doi_str_mv	10.1186/s12964-023-01397-6
title_sort	sars-cov-2 s protein activates nlrp3 inflammasome and deregulates coagulation factors in endothelial and immune cells
title_auth	SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
abstract	Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract © The Author(s) 2024. corrected publication 2024
abstractGer	Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract © The Author(s) 2024. corrected publication 2024
abstract_unstemmed	Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. BJi2XdMkuptrjYtS_YhKHeVideo Abstract © The Author(s) 2024. corrected publication 2024
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container_issue	1
title_short	SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
url	https://dx.doi.org/10.1186/s12964-023-01397-6
remote_bool	true
author2	Alfaro, Enrique Morales, Cristina Díaz-García, Elena López-Fernández, Cristina Bartha, José Luis López-Sánchez, Francisco Lorenzo, Óscar Moncada, Salvador Sánchez-Ferrer, Carlos F. García-Río, Francisco Cubillos-Zapata, Carolina Peiró, Concepción
author2Str	Alfaro, Enrique Morales, Cristina Díaz-García, Elena López-Fernández, Cristina Bartha, José Luis López-Sánchez, Francisco Lorenzo, Óscar Moncada, Salvador Sánchez-Ferrer, Carlos F. García-Río, Francisco Cubillos-Zapata, Carolina Peiró, Concepción
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doi_str	10.1186/s12964-023-01397-6
up_date	2024-07-04T01:25:12.929Z
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