1,25‐Dihydroxyvitamin D₃ increases type 1 interleukin‐1 receptor expression in a murine T cell line

Abstract

The biologically active metabolite of vitamin D3, 1,25 (OH)2 D3, exerts important immunoregulatory effects in addition to being a central mediator of calcium/phosphate metabolism. Utilizing an interleukin 1 responsive murine T cell line and 125I-interleukin 1 alpha, we show that 1,25 (OH)2 D3 (5,50 nM) enhanced 125I-interleukin 1 alpha binding up to almost 2-fold over control. This 1,25 (OH)2 D3 effect occurred in a dose-dependent manner and was detectable after 24 h but not before 7 h of culture. Scatchard analysis of 125I-interleukin 1 alpha binding data demonstrated that 1,25 (OH)2 D3 enhanced interleukin 1 receptor number without a significant change in affinity. The biologically less potent metabolite of vitamin D3, 25 (OH) D3, also augmented 125I-interleukin 1 alpha binding but at steroid levels 2-3 log orders greater than 1,25 (OH)2 D3. This observation, combined with the presence of high-affinity 3H-1,25 (OH)2 D3 receptors (88 sites/cell, K = 0.45 nM) in cytosolic extracts, strongly suggests that the nuclear vitamin D receptor mediates this steroid's effect on interleukin 1 receptor expression. Based on the capacity of an anti-type 1 interleukin 1 receptor monoclonal antibody (35F5) to block 1,25 (OH)2 D3-enhanced 125I-interleukin 1 alpha binding, we conclude that this steroid augments type 1 interleukin 1 receptor expression. When combined with interleukin 1, a cytokine that also impacts MD10 interleukin 1 receptor expression, 1,25 (OH)2 D3 enhanced interleukin 1 receptor expression. Northern blots hybridized with a 32P-type 1 interleukin 1 receptor cDNA probe show that 1,25 (OH)2 D3 enhanced type 1 interleukin 1 receptor steady state mRNA levels. Functionally, 1,25 (OH)2 D3 pretreatment augmented the MD10 proliferative response to suboptimal levels of interleukin 1 (< 100 fM interleukin 1 alpha). These findings further support 1,25 (OH)2 D3's role as an immunoregulatory molecule and provides a possible mechanism by which this steroid could potentiate certain immune activities.

Vitamin D in inflammatory diseases

“…The vitamin D 3 upregulated protein 1 (VDUP1), which is expressed in a 1α,25(OH) 2 D 3 -dependent manner, has been found to inhibit the activity of the IL-3 receptor promoter (Han et al, 2003). On the other hand, IL-1 and IL-4 receptor densities seem to be upregulated by 1α,25(OH) 2 D 3 on a murine T-cell line and a murine osteoblast cell line, respectively (Lacey et al, 1993a,b). Furthermore, downregulated IL-22 mRNA and protein levels have been detected in cultured epidermis tissue treated with calcipotriol, a vitamin D analog (Moniaga et al, 2013).…”

Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence

“…In fact, vitamin D3 has: been shown to have stimulatory effects on various T cell functions including secretion and responsiveness to various cytokines [38][39][40], although immunoinhibitory effects by vitamin D3 have also been reported [40]. Although we have shown that the enhancement in T cell function coincides with vitamin D3 blockage of the capacity of the tumor to maintain myelopoiesis-associated suppressor activity, the possibility that vitamin D3 may have direct immunostimulatory effects on T cell function cannot be excluded.…”