HUMAN NEUTROPHILS EXPRESS MESSENGER RNA OF VITAMIN D RECEPTOR AND RESPOND TO 1α,25-DIHYDROXYVITAMIN D₃

ABSTRACT

1α,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) has been shown to modulate the production of various cytokines or the expression of certain differentiation markers in human T cells or monocytes. Its effects on neutrophils, however, are poorly understood. In this paper, we show several lines of evidence indicating that neutrophils express functional vitamin D receptors (VDR). Sort-purified neutrophils from human peripheral blood expressed VDR mRNA at a level comparable to that of monocytes. As reported to occur in monocytes, protein expression of CD14 on the cell surface of neutrophils was augmented when the cells were incubated with 1,25(OH)₂D₃. To investigate the physiological roles for VDR in neutrophils, we investigated possible modulating effects of 1,25(OH)₂D₃ on the expression of several genes in lipopolysaccharide-stimulated neutrophils by using differential display analysis. Of the genes we identified, trappin-2/elafin/SKALP, which was originally reported to be an inhibitor of elastase, was induced in neutrophils by lipopolysaccharide, but was suppressed significantly in the presence of 1,25(OH)₂D₃. Under the same conditions, interleukin-1β expression was also inhibited. These findings suggest that 1,25(OH)₂D₃ has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.