Renal ischemia/reperfusion (I/R) injury is a major cause of kidney damage. There is accumulating evidence that inflammatory reactions are involved in the pathogenesis of this process. Our studies demonstrate that transgenic mice overexpressing human extracellular and intracellular glutathione peroxidases (GP) are protected against kidney I/R injury. Importantly, significant reduction in neutrophil migration was observed in GP mice compared with nontransgenic mice. Analysis of signaling molecules mediating neutrophil activation and recruitment indicates reduction in the level of KC and macrophage inflammatory protein-2 chemokine expression in transgenic animals. The molecular mechanism mediating this effect appears to involve repression of NF-κB activation at the level of IκBα and IκBβ degradation. In the case of κBα, no apparent phosphorylation was detected. These results suggest that IκBα proteolysis is triggered during the renal I/R pro-oxidant state by a still unknown mechanism, which might be different from other stimuli. A central role of NF-κB in CXC chemokine activation was demonstrated in cell culture anoxia/ATP repletion experiments as a model of I/R. The data presented indicate the important role of GP-sensitive signal transduction pathways in the development of inflammatory response and tissue injury during I/R.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Immunology|
|State||Published - Nov 15 1999|
All Science Journal Classification (ASJC) codes
- Immunology and Allergy