1,25‐Dihydroxyvitamin D 3 increases type 1 interleukin‐1 receptor expression in a murine T cell line

The biologically active metabolite of vitamin D 3 , 1,25 (OH) 2 D 3 , 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 125 I‐interleukin 1α, we show that 1,25 (OH) 2 D 3 (5,50 nM) enhanced 125 I‐interleukin 1α binding up to almost 2‐fold over control. This 1,25 (OH) 2 D 3 effect occurred in a dose‐dependent manner and was detectable after 24 h but not before 7 h of culture. Scatchard analysis of 125 I‐interleukin 1α binding data demonstrated that 1,25 (OH) 2 D 3 enhanced interleukin 1 receptor number without a significant change in affinity. The biologically less potent metabolite of vitamin D 3 , 25 (OH) D 3 , also augmented 125 I‐interleukin 1α binding but at steroid levels 2–3 log orders greater than 1,25 (OH) 2 D 3 . This observation, combined with the presence of high‐affinity 3 H‐1,25 (OH) 2 D 3 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 D 3 ‐enhanced 125 I‐interleukin 1α 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 D 3 enhanced interleukin 1 receptor expression. Northern blots hybridized with a 32 P‐type 1 interleukin 1 receptor cDNA probe show that 1,25 (OH) 2 D 3 enhanced type 1 interleukin 1 receptor steady state mRNA levels. Functionally, 1,25 (OH) 2 D 3 pretreatment augmented the MD10 proliferative response to suboptimal levels of interleukin 1 (< 100 fM interleukin 1α). These findings further support 1,25 (OH) 2 D 3 's role as an immunoregulatory molecule and provides a possible mechanism by which this steroid could potentiate certain immune activities.