RT Journal Article
T1 Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP.
A1 Rico-Llanos, Gustavo
A1 Porras-Perales, Oscar
A1 Escalante, Sandra
A1 Vazquez-Calero, Daniel B
A1 Valiente, Lucia
A1 Castillo, Maria I
A1 Perez-Tejeiro, Jose Miguel
A1 Baglietto-Vargas, David
A1 Becerra, Jose
A1 Reguera, Jose Maria
A1 Duran, Ivan
A1 Csukasi, Fabiana
K1 4-PBA
K1 COVID-19
K1 TNFa
K1 Acute respiratory distress syndrome
K1 Binding-immunoglobulinprotein (BiP/GRP78/HSPA5)
K1 Cell surface GRP78 (csGRP78)
K1 Cellular stress
K1 Cytokine storm
AB 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.
PB Frontiers Researcch Foundation
YR 2022
FD 2022-11-18
LK http://hdl.handle.net/10668/20598
UL http://hdl.handle.net/10668/20598
LA en
NO Rico-Llanos G, Porras-Perales Ó, Escalante S, Vázquez-Calero DB, Valiente L, Castillo MI, et al. Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP. Front Immunol. 2022 Nov 18;13:1054962
NO This study was supported by Junta de Andalucía (Consejería de Salud y Familia) through CV20-81404 and PIGE-0178-2020. Universidad de Málaga and IBIMA-Plataforma Bionand funds (Plan propio UMA and IBIMA-TECH); Ministerio de Ciencia, Innovación y Tecnología (PID2020-117255-RB100). FC is supported by PCI2021-122094-2B and JMPT by FPU19/06951.
DS RISalud
RD Apr 19, 2025