Abstract. Minimal-change nephrotic syndrome (MCNS) is a renal disease characterized by heavy glomerular proteinuria and increased production of cytokines by immune cells. Because of the central role of nuclear factor-κB (NF-κB) in the regulation of cytokine expression, its activity during the relapse and remission phases of steroid-sensitive MCNS was analyzed. During relapse, nuclear extracts from peripheral blood mononuclear cells displayed high levels of NF-κB DNA-binding activity, consisting primarily of p50/RelA (p65) complexes. NF-κB p65 and IκBα proteins were barely detected or not detected in cytosolic fractions during relapse, in contrast to remission. The lack of expression of IκBα protein was associated with downregulation of IκBα mRNA and increases in the levels of the mRNA encoding the proteasome α2 subunit proteolytic pathway. In addition, inhibition of proteasome activity induced cytosolic accumulation of phosphorylated IκBα and significant reductions in the NF-κB binding activity in nuclear extracts from peripheral blood mononuclear cells from patients experiencing relapses. These results suggest that alterations in the NF-κB/IκBα regulatory feedback loop may contribute to the immunologic abnormalities that occur in steroidsensitive MCNS.
Immunoglobulin synthesis by peripheral blood mononuclear cells in minimal change nephrotic syndrome
