%0 Journal Article
%A Rico-Llanos, Gustavo
%A Porras-Perales, Oscar
%A Escalante, Sandra
%A Vazquez-Calero, Daniel B
%A Valiente, Lucia
%A Castillo, Maria I
%A Perez-Tejeiro, Jose Miguel
%A Baglietto-Vargas, David
%A Becerra, Jose
%A Reguera, Jose Maria
%A Duran, Ivan
%A Csukasi, Fabiana
%T Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP.
%D 2022
%U http://hdl.handle.net/10668/20598
%X 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.
%K 4-PBA
%K COVID-19
%K TNFa
%K Acute respiratory distress syndrome
%K Binding-immunoglobulinprotein (BiP/GRP78/HSPA5)
%K Cell surface GRP78 (csGRP78)
%K Cellular stress
%K Cytokine storm
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