Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors
| Autor: | Lukasz Galganski, Hanna Galganska, Wieslawa Jarmuszkiewicz |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Necrosis Anti-Inflammatory Agents Inflammation ERK1 Proinflammatory cytokine Cell Line ERK2 S protein Cellular and Molecular Neuroscience Interferon-gamma Protein Domains Extracellular medicine Human Umbilical Vein Endothelial Cells Humans Protein kinase A Molecular Biology Pharmacology Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Kinase Chemistry SARS-CoV-2 Tumor Necrosis Factor-alpha Interleukin-6 COVID-19 Cell Biology Hydrogen Peroxide Carbon Dioxide Cell biology COVID-19 Drug Treatment Bicarbonate Spike Glycoprotein Coronavirus Molecular Medicine Tumor necrosis factor alpha Original Article medicine.symptom |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 |
| Popis: | Mitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe coronavirus disease 2019 (COVID-19). In this work, we demonstrate that human MAPKs, i.e. extracellular signal-regulated kinases 1 and 2 (ERK1/2), are CO2 sensors and CO2 is an efficient anti-inflammatory compound that exerts its effects through inactivating ERK1/2 in cultured endothelial cells when the CO2 concentration is elevated. CO2 is a potent inhibitor of cellular proinflammatory responses caused by H2O2 or the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. ERK1/2 activated by the combined action of RBD and cytokines crucial for the development of severe COVID-19, i.e. interferon-gamma (IFNγ) and tumour necrosis factor-α (TNFα), are more effectively inactivated by CO2 than by dexamethasone or acetylsalicylic acid in human bronchial epithelial cells. Previously, many preclinical and clinical studies showed that the transient application of 5–8% CO2 is safe and effective in the treatment of many diseases. Therefore, our research indicates that CO2 may be used for the treatment of COVID-19 as well as the modification of hundreds of cellular pathways. |
| Databáze: | OpenAIRE |
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