A recent study that sought to understand the role of temperature in inflammatory response found that temperature regulates NF-κB dynamics. Just a slight rise in temperature, such as a fever, speeds up a cellular “clock” in which proteins switch genes on and off, according to a multidisciplinary team of mathematicians and biologists from the Universities of Warwick and Manchester.
In the study, published last week in PNAS, the team found that inflammatory signals activate NF-κB proteins to start the “clock” ticking, in which NF-κB proteins move backwards and forwards into and out of the cell nucleus, where they switch genes on and off. This allows cells to respond to a tumor, wound, or infection.
At a body temperature of 34 degrees, the NF-κB clock slows down. At higher temperatures than the normal 37 degree body temperature, the NF-κB clock speeds up.
When NF-κB is uncontrolled, it is associated with inflammatory diseases, such as Crohn's disease, psoriasis, and rheumatoid arthritis.
The researchers also found that when they removed the protein A20 from cells that the NF-kB clock lost its sensitivity to increases in temperature. According to the team, this discovery suggests that new drugs might more precisely change the inflammatory response by targeting the A20 protein.
While the activities of many NF-kB controlled genes were not affected by temperature, a key group of genes showed altered profiles at the different temperatures. These temperature sensitive genes included key inflammatory regulators and controllers of cell communication that can alter cell responses.