Potentiation of Lipopolysaccharide - Induced Tumor Necrosis Factor - cw

The immunomodulatory hormone 1.25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as 6-cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1f3 in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(0H)2D~. We now show that 1,25-(OH)zD3 also primes the increase in U937 cell tumor necrosis factor (TNF)-a-accumulated mRNA after activation with LPS; 50% effective concentration (ECso) for the LPS-induced expression of TNF-a mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25-(OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-a mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(Oti)2D3 because dexamethasone