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Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Mol+Life+Sci 2021 ; 78 (24): 8229-8242 Nephropedia Template TP
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Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors #MMPMID34741187
Galganska H; Jarmuszkiewicz W; Galganski L
Cell Mol Life Sci 2021[Dec]; 78 (24): 8229-8242 PMID34741187show ga
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 CO(2) sensors and CO(2) is an efficient anti-inflammatory compound that exerts its effects through inactivating ERK1/2 in cultured endothelial cells when the CO(2) concentration is elevated. CO(2) is a potent inhibitor of cellular proinflammatory responses caused by H(2)O(2) 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 (IFNgamma) and tumour necrosis factor-alpha (TNFalpha), are more effectively inactivated by CO(2) 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% CO(2) is safe and effective in the treatment of many diseases. Therefore, our research indicates that CO(2) may be used for the treatment of COVID-19 as well as the modification of hundreds of cellular pathways.
|*COVID-19 Drug Treatment[MESH]
|Anti-Inflammatory Agents/*pharmacology[MESH]
|COVID-19/immunology/pathology[MESH]
|Carbon Dioxide/*pharmacology[MESH]
|Cell Line[MESH]
|Human Umbilical Vein Endothelial Cells[MESH]
|Humans[MESH]
|Hydrogen Peroxide/toxicity[MESH]
|Inflammation/drug therapy[MESH]
|Interferon-gamma/drug effects[MESH]
|Mitogen-Activated Protein Kinase 1/*antagonists & inhibitors/metabolism[MESH]
|Mitogen-Activated Protein Kinase 3/*antagonists & inhibitors/metabolism[MESH]