Identifying a role for cellular CO2 sensor

The levels of oxygen (O₂) and carbon dioxide (CO₂) in cells can vary dramatically in health and in diseases such as chronic inflammation, ischemia and cancer where metabolism rates are significantly altered. Elevated CO₂ levels that occur during hypoventilation of intubated patients have been found to decrease mortality associated with acute respiratory distress syndrome or endotoxin-induced acute lung injury.

Acute CO₂ sensing is a feature of specialised cells in lower animal species such as flies and rodents but little is known about the effect of altered CO₂ on gene expression. This research group, led by Conway fellow, Professor Cormac Taylor examined the effect of altered CO₂ levels on gene expression in mammalian cells against a background of inflammation.

“Our results suggest that a molecular CO₂ sensor associated with anti-inflammatory and immunosuppressive signalling may exist. We found that elevated levels of CO₂ had a profound effect on a master signalling pathway called NF-ĸB”, said Dr. Eoin Cummins, postdoctoral researcher and lead author on this publication.

In previous work, the Taylor group demonstrated that the NF-ĸB master signalling pathway is induced by hypoxic (low O₂) conditions. In this study, the researchers now show that a central protein regulator within this pathway, IKKα reacts to CO₂ levels in a rapid, reversible and dose dependent manner.

Commenting on the significance of the research, Dr. Cummins said, “The molecular mechanism of this CO₂ sensor may provide an alternative therapeutic route in those instances when suppressing the body’s innate immune system or inflammatory response is clinically desirable. We now need to decipher the exact mechanisms of this CO₂-dependent intracellular signalling pathway”.

More information: NF-{kappa}B links CO₂ sensing to innate immunity and inflammation in mammalian cells. Eoin P. Cummins, et al. doi:10.4049/jimmunol.1000701

Provided by University College Dublin