Redox Regulation of Cytokine Expression in Kupffer Cells

Kupffer cells, resident macrophages in the liver, play a central role in the homeostatic response to liver injury. Ironically, this defensive mechanism, if dysregulated, also works against the liver in acute and chronic liver damage. Central to this response is activation of nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor that transactivates promoters of many inflammatory genes, including cytokines. Much research has been devoted to identification of upstream signaling for activation of NF-kappaB, but the precise mechanism by which oxidant stress participates in this signaling is yet to be determined. Clues to this key question may be attained through studies on the mechanisms of sustained and/or accentuated NF-kappaB activation in hepatic macrophages in chronic liver diseases. This article reviews the literature on redox regulation of cytokine gene expression by Kupffer cells.