Carbon dioxide and MAPK signalling: towards therapy for inflammation

Area of Science:

• Biochemistry and Molecular Biology
• Immunology
• Pathophysiology

Background:

• Inflammation is a critical immune response but can become harmful when dysregulated, contributing to numerous diseases.
• Mitogen-activated protein kinases (MAPKs) play a central role in cellular responses to infection, inflammation, and diseases like COVID-19.
• Comorbidities and advanced age exacerbate viral infections, with COVID-19 highlighting the severe impact of inflammation and MAPK signaling.

Discussion:

• Carbon dioxide (CO2) is increasingly recognized as a regulator of MAPK pathways.
• This review explores the literature for associations between CO2 and MAPKs, focusing on therapeutic potential.
• The interplay between CO2, MAPKs, and inflammation is examined in various disease contexts, including metabolic disorders and post-COVID-19 complications.

Key Insights:

• CO2 directly influences key processes involved in inflammation and its resolution.
• Therapeutic effects of elevated CO2 (or bicarbonate) are observed in conditions where MAPKs are implicated, such as diabetes, obesity, and hypertension.
• Signaling pathways of MAPKs and CO2 overlap in critical cellular functions like apoptosis, cell survival, and lung responses.

Outlook:

• Further research into CO2-mediated regulation of MAPKs could reveal novel therapeutic strategies.
• Understanding these pathways may lead to improved management of inflammatory diseases and COVID-19 sequelae.
• Investigating CO2's role in mitochondrial function and cellular respiration offers new avenues for treatment development.