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10.1016/j.jbc.2022.101695 http://scihub22266oqcxt.onion/10.1016/j.jbc.2022.101695 35143839!8820157!35143839     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2022 ; 298 (3): 101695 Nephropedia Template TP {{tp|p=35143839|t=2022. The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling |pdf=|usr=}}{{35143839}} gab.com Text The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=35143839 #FOAvip Vascular endothelial cells (ECs) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, hallmarks of this severe disease. However, the mechanisms by which ECs are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin ?5beta1 signaling. Incubation of human umbilical vein ECs with whole spike protein, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-kappaB and subsequent expression of leukocyte adhesion molecules (VCAM1 and ICAM1), coagulation factors (TF and FVIII), proinflammatory cytokines (TNFalpha, IL-1beta, and IL-6), and ACE2, as well as the adhesion of peripheral blood leukocytes and hyperpermeability of the EC monolayer. In addition, inhibitors of integrin ?5beta1 activation prevented these effects. Furthermore, these vascular effects occur in vivo, as revealed by the intravenous administration of spike, which increased expression of ICAM1, VCAM1, CD45, TNFalpha, IL-1beta, and IL-6 in the lung, liver, kidney, and eye, and the intravitreal injection of spike, which disrupted the barrier function of retinal capillaries. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin ?5beta1 in ECs to activate the NF-kappaB target gene expression programs responsible for vascular leakage and leukocyte adhesion. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin ?5beta1 as a promising target for treating vascular inflammation in COVID-19. Twit Text FOAVip The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=35143839 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35143839 #FOAvip English Wikipedia <ref>{{Cite pmid|35143839}}</ref> The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling #MMPMID35143839 Robles JP; Zamora M; Adan-Castro E; Siqueiros-Marquez L; Martinez de la Escalera G; Clapp C J Biol Chem 2022[Mar]; 298 (3): 101695 PMID35143839show ga Vascular endothelial cells (ECs) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, hallmarks of this severe disease. However, the mechanisms by which ECs are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin ?5beta1 signaling. Incubation of human umbilical vein ECs with whole spike protein, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-kappaB and subsequent expression of leukocyte adhesion molecules (VCAM1 and ICAM1), coagulation factors (TF and FVIII), proinflammatory cytokines (TNFalpha, IL-1beta, and IL-6), and ACE2, as well as the adhesion of peripheral blood leukocytes and hyperpermeability of the EC monolayer. In addition, inhibitors of integrin ?5beta1 activation prevented these effects. Furthermore, these vascular effects occur in vivo, as revealed by the intravenous administration of spike, which increased expression of ICAM1, VCAM1, CD45, TNFalpha, IL-1beta, and IL-6 in the lung, liver, kidney, and eye, and the intravitreal injection of spike, which disrupted the barrier function of retinal capillaries. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin ?5beta1 in ECs to activate the NF-kappaB target gene expression programs responsible for vascular leakage and leukocyte adhesion. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin ?5beta1 as a promising target for treating vascular inflammation in COVID-19. |*COVID-19/metabolism/pathology/virology[MESH] |*Inflammation/metabolism/pathology/virology[MESH] |*Integrin alpha5beta1/metabolism[MESH] |*NF-kappa B/metabolism[MESH] |*Spike Glycoprotein, Coronavirus/metabolism[MESH] |*Tumor Necrosis Factor-alpha/metabolism[MESH] |Human Umbilical Vein Endothelial Cells[MESH] |Humans[MESH] |Interleukin-6/metabolism[MESH] |Oligopeptides[MESH] |SARS-CoV-2[MESH]The spike protein of SARS-CoV-2 induces endothelial inflammation throu(epmc).pdf DeepDyve Pubget Overpricing