In their report in the March 1 issue of the Journal of Clinical Investigation, John Engelhardt and colleagues from the University of Iowa observed that mice in which I kappa B alpha has been replaced by I kappa B beta have identical levels of liver NF-kappa B activation in response to lipopolysaccharide-induced injury, while a significantly reduced level of liver NF-kappa B activation was observed in response to liver ischemia and reperfusion. The data suggest that while either I kappa B alpha and I kappa B beta can mediate responses to lipopolysaccharide, I kappa B alpha is essential for mediating liver ischemia/reperfusion injuries.

Further studies suggested that the specificity of I kappa B alpha, but not I kappa B beta, in the regulation of NF-kappa B induction during ischemia/reperfusion injury is due to the injury-contextspecific activation of c-Src and subsequent phosphorylation of an I kappa B alpha tyrosine residue, Tyr42. While this signaling pathway was previously known, the authors have uncovered the pathway's physiological significance. The authors also suggest that down-regulation of I kappa B alpha expression following liver ischemia/reperfusion injury may be therapeutically beneficial.

TITLE: I kappa B alpha and I kappa B beta possess injury contextspecific functions that uniquely influence hepatic NF-kappa B induction and inflammation

AUTHOR CONTACT:
John F. Engelhardt
University of Iowa, Iowa City, Iowa, USA.
Phone: 319-335-7744
Fax: 319-335-6581
E-mail: john-engelhardt@uiowa.edu

View the PDF of this article at: https://www.the-jci.org/pr
'"/>

Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
1-Mar-2004