VDR Pathway-Specific Dose-Related Effects of 1,25(OH)2D3 on Salmonella typhimurium-induced Mouse Colitis

Abstract

Background: Whether and how 1,25(OH)2D3 supplementation influences VDRs in experimental mice with colitis remains to be seen. To explore the effect of 1,25(OH)2D3 on S. typhimurium colitis through the VDR pathway and to discover the role of VDR in its action. Methods: We established a mouse UC model induced by S. typhimurium. After streptococcal typhus infection, the mice were fasted for 12 hours. Blood was collected by the eyeball extraction method, and then sacrificed by cervical dislocation, specimens were collected for corresponding indicators. Results: Mice exposed to S. typhimurium infection developed signs of acute colitis. After HE staining were performed on the diseased colons from the mice. high dose VD supplementation, the pathological colonic damage did not improve in the mice, and there was no statistical difference between the groups with VD deficiency (P>0.05). VDR expression in the UC group treated with Salmonella was higher than that in the control group, a statistically significant difference (P<0.01). Compared with the VDD+UC group, VDR expression rose in both the LVDS+UC group and the HVDS+UC group, with VDR protein expression being highest after high dose VD supplementation (P<0.01). Compared with the control and the UC groups, the VDR mRNA expression level in the VDD+UC group was significantly higher, and the colon VDR mRNA expression level decreased after active VD supplementation (Fig.7C). Conclusions: Our data suggest the need for defining the accurate 1,25(OH)2D3 dose limits that induce an anti-inflammatory effect as current data indicate that higher doses would produce an inflammatory response.