ArticlePloS one2025
The recombinant spike S1 protein induces injury and inflammation in co-cultures of human alveolar epithelial cells and macrophages.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue.European journal of clinical investigation · 2026Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The current lack of a straightforward and convenient modeling approach to simulate the onset of acute lung injury (ALI) has impeded fundamental research and hindered the screening of therapeutic drugs in coronavirus disease 2019 (COVID-19). The co-cultured human pulmonary alveolar epithelial cells (HPAEpics) and alveolar macrophages (AMs) were exposed to the complete medium, three concentrations of recombinant spike S1 protein (0.1, 1, and 10 μg/mL), or lipopolysaccharide (LPS) (10 μg/mL). The cells were harvested at 1, 2, and 3 days post-exposure. Lactate dehydrogenase (LDH) release, and IL-6, TNF-ɑ, and malondialdehyde (MDA) production were quantified and compared. Compared to those exposed to medium, co-cultures of HPAEpics and AMs exposed to a concentration of S1 protein at 10 μg/mL demonstrated significantly increased levels of LDH release (22.9% vs. 9.1%, and 25.7%), IL-6 (129 vs. 74, and 110 pg/mg of protein), and TNF-ɑ (75 vs. 51, and 86 pg/mg of protein) production, and similar to those exposed to LPS. However, no statistically significant differences were observed in MDA production. Compared to those harvested at 1 or 2 days post-exposure, co-cultured cells harvested at 3 days post-exposure exhibited increased levels of LDH release (23.4% vs. 14.9%, or 16.7%), IL-6 (127 vs. 81, or 97 pg/mg of protein) and MDA (5.6 vs. 3.2, or 3.8 nmol/mg of protein) production, but exhibited lower TNF-ɑ (58 vs. 79 pg/mg of protein) production than those harvested at 2 days post-exposure. After 3 days of exposure, co-cultures of HPAEpics and AMs showed significantly increased levels of LDH release (25.3% vs. 18.4%), and MDA production (5.5 vs. 4.3 nmol/mg of protein) compared to HPAEpics monocultures, and increased levels of LDH release (25.3% vs. 13.8%), IL-6 (139 vs. 98 pg/mg of protein) and MDA (5.5 vs. 4.7 nmol/mg of protein) production, and decreased TNF-ɑ (59 vs. 95 pg/mg of protein) production compared to AMs monocultures. Conclusions: The exposure to a concentration of S1 protein at 10 μg/mL in co-cultures of HPAEpics and AMs induced significant injury and inflammation three days post-exposure. This methodology for establishing a COVID-19-associated ALI model may have promising potential applications and value.
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