Nuclear factor-κB in pancreatitis: Jack-of-all-trades, but which one is more important?

Abstract

See “Deletion of IκBα activates RelA to reduce acute pancreatitis in mice through up-regulation of Spi2A,” by Neuhöfer P, Liang S, Einwächter H, et al, on page 192; and “Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice,” by Huang H, Liu Y, Daniluk J, et al, on page 202.

Figure 1

Pathways through which acinar cell NF-κB activation regulates inflammation in pancreatitis. A major proinflammatory mechanism is the induction of cytokines and other mediators, as emphasized by Huang et al. In contrast, Neuhöfer et al emphasize the protective effect of NF-κB against acinar cell necroptosis, limiting pancreatic inflammation. The mechanisms underlying this prosurvival effect of NF-κB are not clear but may involve PAP1, Spi2A, Bcl-xL, and other proteins. One mechanism whereby acinar cell necrosis may promote pancreatic inflammation is through activation of the inflammasome.^, The protective effect of NF-κB activation could also be through limiting IL-1β processing and secretion.