2026-08-29T14:17:51Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/188552024-09-21T21:04:29Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Rico-Llanos, Gustavo author Porras-Perales, Óscar author Escalante, Sandra author Vázquez-Calero, Daniel B author Valiente, Lucía author Castillo, María I author Pérez-Tejeiro, José Miguel author Baglietto-Vargas, David author Becerra, José author Reguera, José María author Duran, Ivan author Csukasi, Fabiana 2024-02-27T15:24:38Z 2024-02-27T15:24:38Z 2022-11-18 10.3389/fimmu.2022.1054962 1664-3224 Frontiers in immunology http://hdl.handle.net/10668/20598 36466830 http://hdl.handle.net/20.500.12105/18855 Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we observed increased levels of cell surface BiP (cs-BiP) in leukocytes during inflammation. This corresponds with a higher number of neutrophiles, which show naturally high levels of cs-BiP, whereas alveolar macrophages show a higher than usual exposure of BiP in their cell surface. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs. eng 4-PBA COVID-19 TNFa acute respiratory distress syndrome binding-immunoglobulinprotein (BiP/GRP78/HSPA5) cell surface GRP78 (csGRP78) cellular stress cytokine storm Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP. research article