Increased ER Stress and Unfolded Protein Response Activation in Epithelial and Inflammatory Cells in Hypersensitivity Pneumonitis
Por:
Cabrera, S, Garcia-Vicente, A, Gutierrez, P, Sanchez, A, Gaxiola, M, Rodriguez-Bobadilla, C, Selman, M, Pardo, A
Publicada:
1 may 2024
Ahead of Print:
1 may 2024
Resumen:
Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP:
Filiaciones:
Cabrera, S:
Univ Nacl Autonoma Mexico, Fac Sci, Dept Cell Biol, Fibrosis Lab, Exterior Circuit S-N,CU,Coyoacan, Mexico City 04510, Mexico
Garcia-Vicente, A:
Univ Nacl Autonoma Mexico, Unidad Biopatol Pulm, Lab Fibrosis, Ciencias INER, Mexico City, Mexico
Gutierrez, P:
Univ Nacl Autonoma Mexico, Unidad Biopatol Pulm, Lab Fibrosis, Ciencias INER, Mexico City, Mexico
Gaxiola, M:
Inst Nacl Enfermedades Respiratorias Ismael Cosio, Mexico City, Mexico
Rodriguez-Bobadilla, C:
Univ Nacl Autonoma Mexico, Unidad Biopatol Pulm, Lab Fibrosis, Ciencias INER, Mexico City, Mexico
Selman, M:
Inst Nacl Enfermedades Respiratorias Ismael Cosio, Mexico City, Mexico
Pardo, A:
Univ Nacl Autonoma Mexico, Unidad Biopatol Pulm, Lab Fibrosis, Ciencias INER, Mexico City, Mexico
hybrid, All Open Access; Hybrid Gold Open Access
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