The anti-inflammatory activity of 1,25-dihydroxyvitamin D3 in macrophages

Merav Cohen-Lahav, Amos Douvdevani, Cidio Chaimovitz, Shraga Shany

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

In a previous study we demonstrated a down-regulatory effect of vitamin D active metabolite (1,25(OH)2D3) and its vitamin D2 analog (1,24(OH)2D2) on TNFα expression in macrophages. We also found an inhibitory effect in the physiological concentration (10-10 M) of 1,25(OH)2D3 which was dose-dependent. This down-regulation, caused by the decrease in NFκB activity by 1,25(OH)2D3 and 1,24(OH)2D2, was demonstrated in P388D1 cells transfected with NFκB reporter gene (p NFκB-Luc) and by EMSA. In our present study we investigated the processes leading to reduced NFκB activity on P388D1 cells. A decrease in nuclei NFκB-p65 and an increase in cytosolic NFκB-p65, were measured, while no changes in total NFκB-p65 mRNA and protein levels were observed. Simultaneously, a significant increase in both mRNA and protein levels of the NFκB-cytosolic inhibitor, IκBα, were determined. The half-life of IκBα-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)2D3 and 1,24(OH)2D2 inhibit TNFα expression in macrophages, by increasing IκBα and decreasing NFκB activity. Since NFκB is a major transcription factor for TNFα and other inflammatory mediators, these findings suggest that 1,25(OH)2D3 and 1,24(OH)2D2 may be used therapeutically as anti-inflammatory agents.

Original languageEnglish
Pages (from-to)558-562
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
DOIs
StatePublished - 1 Mar 2007

Keywords

  • Anti-inflammatory
  • IκBα
  • Macrophages
  • NFκB
  • TNFα
  • Vitamin D analog

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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