RETRACTED: The anti-inflammatory activity of 1,25-dihydroxyvitamin D3 in macrophages (Retracted article. See vol. 127, pg. 444, 2011)

In a previous study we demonstrated a down-regulatory effect of vitamin D active metabolite (1,25(OH)(2)D-3) and its vitamin D, analog (1,24(OH)(2)D-2) on TNF alpha expression in macrophages. We also found an inhibitory effect in the physiological concentration (10(-10) M) of 1,25(OH)(2)D-3 which was dose-dependent. This down-regulation, caused by the decrease in NF kappa B activity by 1,25(OH)(2)D-3 and 1,24(OH)(2)D-2, was demonstrated in P388D1 cells transfected with NF kappa B reporter gene (p NF kappa B-Luc) and by EMSA. In our present study we investigated the processes leading to reduced NF kappa B activity on P388D1 cells. A decrease in nuclei NF kappa B-p65 and an increase in cytosolic NF kappa B-p65, were measured, while no changes in total NF kappa B-p65 mRNA and protein levels were observed. Simultaneously, a significant increase in both mRNA and protein levels of the NF kappa B-cytosolic inhibitor, I kappa B alpha, were determined. The half-life of I kappa B alpha-mRNA increased, with a parallel decrease in the phosphorylation of its protein, as the first step of ubiquitinization and degradation. The present results demonstrate that 1,25(OH)(2)D-3 and 1,24(OH)(2)D-2 inhibit TNF alpha expression in macrophages, by increasing I kappa B alpha and decreasing NF kappa B activity. Since NF kappa B is a major transcription factor for TNF alpha and other inflammatory mediators, these findings suggest that 1,25(OH)(2)D-3 and 1,24(OH)(2)D-2 may be used therapeutically as anti-inflammatory agents. (c) 2006 Elsevier Ltd. All rights reserved.