Albumin in the mg/1-range activates NF-kappa B in renal proximal tubule-derived cell lines via tyrosine kinases and protein kinase C

Albuminuria represents one of the most unfavourable diagnostic factors for the prognosis of nephropathies. We investigated albumin-induced NF-kappaB activation and the potential cont ribution of tyrosine kinase and protein kinase C. Therefore we exposed prox imal tubule-derived human (IHKE-1), opossum (OK) and porcine (LLC-PK1) cell lines to serum albumin at concentrations of 10-500 mg/l. DNA-binding activity of NF-kappaB increased concentration-dependently in th e presence of albumin. In OK and LLC-PK1 cells, NF-kappaB activity increase d during the first 45 min and reached a plateau thereafter. In IHKE-1, cell s NF-kappaB activity reached a plateau after 90 min with a maximum at 180 m in exposure to albumin. The albumin-induced increase in NF-kappaB DNA-bindi ng activity was inhibited by herbimycin A (tyrosine kinase inhibitor) and B IM (protein kinase C inhibitor). Reporter gene assays demonstrated that alb umin stimulates NF-kappaB mediated reporter gene activation in LLC-PK1 cell s, which was partially inhibited by herbimycin A and BIM. Our data indicate, that albumin exposure induces a rapid increase in NF-kap paB protein activity in renal proximal tubule cells of different species vi a a tyrosine kinase- and protein kinase C-dependent pathway, at concentrati ons occurring during mild glomerular injury.