Activation of RelA (p65), but not of p50 dimers of nuclear factor kappa B (NF‐κB) is decreased in impaired renal function

Abstract

The NF‐κB signaling pathway plays a central role in chronic inflammation and is an important interface between inflammation and oxidative stress. The heterodimer RelA (p65) ‐ p50 is the most abundant transcription factor of the NF‐κB family. Decreased activation of RelA has been found in different pathologies. The purpose of this study of the BIOCLAIMS project was to investigate the activation of both the RelA and p50 dimers in individuals with different stages of renal function. Peripheral blood mononuclear cells (PBMC) were collected from 362 study subjects with glomerular filtration rate (GFR, MDRD) of 18–123 mL/min/1.73 m2. Activation of NF‐κB dimers containing RelA and p50 was determined using an ELISA‐based assay (TransAM, Active Motif). Linear regression analysis showed that activation of RelA‐containing NF‐κB dimers decreased significantly with decreasing GFR (r = 0.171, P = 0.001), while activation of p50‐containing NF‐κB dimers increased significantly with decreasing GFR (r = − 0.148, P = 0.005). Antioxidant status, including plasma concentrations of vitamin C, α‐ and γ‐tocopherol and β‐carotene did not explain NF‐κB activation beyond kidney function. To our knowledge this is the first report on differential effects of impaired renal function on RelA and p50 activation. The underlying mechanisms of these findings need to be further elucidated.Grant Funding Source: Supported by European Commission, FP7, contract 244995, and Austrian Government (bmwf).