Faculty of Biology, Molecular Biology Techniques Laboratory, Adam Mickiewicz University in Poznan, Uniwersytetu Poznanskiego 6, 61-614, Poznan, Poland.
Faculty of Biology, Department of Bioenergetics, Adam Mickiewicz University in Poznan, Institute of Molecular Biology and Biotechnology, Uniwersytetu Poznanskiego 6, 61-614, Poznan, Poland.
Cell Commun Signal. 2023 Oct 10;21(1):280. doi: 10.1186/s12964-023-01306-x.
Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of the immune system to control it. In addition, inflammation is a cause and/or symptom of many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities and advanced age are typical predictors of more severe cases of seasonal viral infection, with COVID-19 a clear example. The primary importance of mitogen-activated protein kinases (MAPKs) in the course of COVID-19 is evident in the mechanisms by which cells are infected with SARS-CoV-2; the cytokine storm that profoundly worsens a patient's condition; the pathogenesis of diseases, such as diabetes, obesity, and hypertension, that contribute to a worsened prognosis; and post-COVID-19 complications, such as brain fog and thrombosis. An increasing number of reports have revealed that MAPKs are regulated by carbon dioxide (CO); hence, we reviewed the literature to identify associations between CO and MAPKs and possible therapeutic benefits resulting from the elevation of CO levels. CO regulates key processes leading to and resulting from inflammation, and the therapeutic effects of CO (or bicarbonate, HCO) have been documented in all of the abovementioned comorbidities and complications of COVID-19 in which MAPKs play roles. The overlapping MAPK and CO signalling pathways in the contexts of allergy, apoptosis and cell survival, pulmonary oedema (alveolar fluid resorption), and mechanical ventilation-induced responses in lungs and related to mitochondria are also discussed. Video Abstract.
炎症虽然对于对抗感染是必要的，但当它超出免疫系统的控制能力时，就会成为一种威胁。此外，炎症是许多不同疾病的原因和/或症状，包括代谢、神经退行性、自身免疫和心血管疾病。合并症和高龄是季节性病毒感染更严重病例的典型预测因素，COVID-19 就是一个明显的例子。丝裂原活化蛋白激酶（MAPKs）在 COVID-19 中的主要重要性在细胞感染 SARS-CoV-2 的机制中显而易见；细胞因子风暴会严重恶化患者的病情；糖尿病、肥胖症和高血压等导致预后恶化的疾病的发病机制；以及 COVID-19 后的并发症，如脑雾和血栓形成。越来越多的报告表明，MAPKs 受到二氧化碳（CO）的调节；因此，我们查阅了文献，以确定 CO 与 MAPKs 之间的关联，以及 CO 水平升高可能带来的治疗益处。CO 调节着导致炎症的关键过程，CO（或碳酸氢盐，HCO）的治疗效果已在 COVID-19 所有上述合并症和并发症中得到证实，其中 MAPKs 发挥作用。在过敏、细胞凋亡和细胞存活、肺水肿（肺泡液吸收）以及与线粒体相关的肺机械通气诱导反应的背景下，重叠的 MAPK 和 CO 信号通路也进行了讨论。视频摘要。
