ABSTRACT
BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.
Subject(s)
Colitis , Humans , Mice , Animals , Colitis/chemically induced , Colitis/drug therapy , Colitis/prevention & control , Inflammation/drug therapy , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Cholecalciferol/therapeutic use , Oxidative Stress , Dextran Sulfate/pharmacology , Mice, Inbred C57BL , Hydroxymethylglutaryl-CoA SynthaseABSTRACT
Atmospheric particles, especially water-soluble inorganic ions are hazardous to human body. Motor vehicle exhaust is the greatest contributor to atmosphere pollution in Tianjin. In order to explore the emission characteristics of different road types, PM2.5 and PM10 from four types of roads were sampled and analyzed by water-soluble ions component analysis and Pearson correlation analysis during the period of April to May, 2015 to discover the ratio of PM2.5 to PM10 and the major pollutants. The results showed that water-soluble inorganic ions mainly existed in fine particles varying with different road types, which mainly came from secondary pollution. The quantities of secondary ions in PM2.5 were twice as high as that in PM10, which were the key components of the water-soluble inorganic ions. This was probably due to the increase of automobiles and their emissions, as well as the transmission and spreading of pollutants in the surroundings. Furthermore, water-soluble inorganic ions might exist in the forms of NaNO3, NH4Cl, NH4NO3, (NH4)2SO4, KCl, KNO3, K2SO4, MgCl2, CaCl2, etc. K+, Mg2+, Na+and Ca2+ showed high homology and the contributors of PM2.5 and PM10 were mainly the mixture of combustion and secondary pollutants, then followed by the mixture of re-suspended dust and traffic source.
