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

Abstract

1Alpha,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-1beta 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.

Invitro Study of Role of Vitamin D on Macrophages Dysfunction in Patients With Diabetic Foot Infection.

“…However the basic question was not answered if vitamin D receptor on macrophage could presumably be responsible for the phagocytosis [15][16][17]. The present study was designed in vitro to demonstrate that the MDM from the diabetic patient having decreased phagocytic activity, improved their function on addition of vitamin D.…”

Vitamin D insufficiency: implications for the immune system

“…Within the immune system, VDR is expressed by almost all immune cells, including activated CD4+ and CD8+ T cells, B cells, neutrophils, and antigenpresenting cells (APCs), such as macrophages and dendritic cells (DCs) [11][12][13]. In addition, the key enzymes needed for vitamin D activation and degradation are expressed by certain immune cells.…”

Innate Immune Modulation in Chronic Obstructive Pulmonary Disease: Moving Closer toward Vitamin D Therapy

“…Expression of both CYP27B1 and VDR has been found in various cell types of the lung innate immune system, including airway epithelial cells, macrophages, and neutrophils (Provvedini et al, 1983;Monkawa et al, 2000;Overbergh et al, 2000;Takahashi et al, 2002;Hansdottir et al, 2008). Consequently, conversion of 25-hydroxyvitamin D into the biologically active 1,25-dihydroxyvitamin D can occur locally in the lungs and in this way act in an autocrine or paracrine fashion to exert its immunomodulatory functions.…”

“…The inhibitory effect of 1,25-dihydroxyvitamin D signaling on major inflammatory pathways results in the decreased expression of proinflammatory cytokines and chemokines in macrophages, dendritic cells, neutrophils, and airway epithelial cells (Takahashi et al, 2002;Hansdottir et al, 2010;Korf et al, 2012;Zhang et al, 2012;Ferreira et al, 2014) (Fig. 1).…”

“…Interestingly, the active form of vitamin D has been shown to exert anti-inflammatory effects by inhibiting NF-kB and MAPK activity (Takahashi et al, 2002;Hansdottir et al, 2010;Zhang et al, 2012) (Fig. 1).…”