Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats

Abstract

Vitamin D3 has been reported to be an immunity modulator and high levels of vitamin D3 are correlated with a decreased risk for developing diseases in the central nervous system. Astrocytes are important immune cells and contribute toward inflammation during neurological diseases. The vitamin D receptor has been reported to be expressed in astrocytes; however, the effect of vitamin D3 on astrocyte activation has not been studied. Here, we found that lipopolysaccharide stimulation in astrocytes could enhance the expression of vitamin D receptor and Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form. Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis factor-α, interleukin-1β, vascular endothelial growth factor, and also TLR4 in activated astrocytes. Astrocyte activation was further found to be suppressed after the administration of vitamin D3 in neonatal rats injected with lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin D3 in astrocytes after lipopolysaccharide stimulation. Considering the function of reactive astrocytes in augmenting inflammatory response in neurodegeneration and brain injury, the finding that vitamin D3 administration may inhibit astrocyte activation may be potentially useful for the treatment of central nervous system disorders.

Focus on 1,25-Dihydroxyvitamin D3 in the Peripheral Nervous System

“…In contrast, vitamin D suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and TLR4 in vivo . These results support a function of reactive astrocytes in stimulating the inflammatory response in neurodegeneration and brain injury and a putative role of vitamin D (Jiao et al, 2017).…”

“…Astrocytes, which are VDR expressing cells, are important immune cells and contribute to inflammation during neurological disorders. Jiao et al (2017) reported that lipopolysaccharide-stimulated neuroinflammation in astrocytes could enhance the expression of the VDR and Cyp27B1. In contrast, vitamin D suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and TLR4 in vivo .…”

Anti-inflammatory effects induced by ultralow concentrations of bupivacaine in combination with ultralow concentrations of sildenafil (Viagra) and vitamin D3 on inflammatory reactive brain astrocytes

“…We searched for a substance with properties to suppress the expression of inflammatory receptors and any substance that could reduce the damage to the BBB. Interestingly, vitamin D3 has these properties [22,23,45]. In addition, astrocytes express the vitamin D3 receptor VDR [46].…”

“…Vitamin D3 stimulates its receptor, vitamin D receptor (VDR), on all neuronal cells, including astrocytes [20]. Furthermore, vitamin D3 has neuroprotective roles through its influence on the expression of nitric oxide synthase (iNOS), which in turn affects nitric oxide (NO) [20], decreases TLR4 expression on astrocytes [21,22] and reduces BBB damage [23].…”

Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog

“…The regulatory role of VitD in adaptive immune response also includes an inhibitory effect on DCs maturation and differentiation ( 28 ) and a Foxp3 + Tregs expansion ( 29 ). Direct immunomodulatory effects of VitD on CNS cells such as neural stem cells ( 30 ), astrocytes ( 31 ), and microglial cells ( 32 ) have been recently reported. VitD analogs with similar VitD immunomodulatory attributes but devoid of its side effects such as hypercalcemia and hyperphosphatemia have been developed ( 33 – 35 ).…”