Role of vitamin D in the onset, progression, and severity of multiple sclerosis.

OBJECTIVE: To review and assess the role of vitamin D in the onset, progression, and relapse of multiple sclerosis (MS), based on evidence acquired from the analysis of preclinical, observational, and interventional studies. METHODS: All English language literature in MEDLINE (January 1969 through April 2012) was searched for observational and interventional studies on the dosage effect of vitamin D on the onset, progression, and relapse rate of MS. The medical subject heading (MeSH) terms used in the search included Vitamin D and Multiple Sclerosis. Additional publications and abstracts were identified from review articles and from the references cited in the previously found articles. In addition to the experimental studies, only those human studies that specified the population size, doses of vitamin D used, and the resulting effect on MS were considered. RESULTS: Vitamin D deficiency is very common among MS patients. Multiple preclinical studies have shown that vitamin D is a potent regulator of inflammation in MS. Most observational studies support an association between high vitamin D levels and a reduced risk of developing MS. However, conflicting results have been reported by observational studies on the correlation between vitamin D and MS severity and by interventional studies using vitamin D as a therapeutic agent for MS. CONCLUSION: Vitamin D deficiency in MS patients should be avoided. In addition, the risk of developing MS might be reduced by maintaining optimal vitamin D levels in the healthy population. Larger randomized interventional trials are needed to clarify the therapeutic effect of vitamin D in MS.

Inhibition of apolipoprotein A-I gene by the aryl hydrocarbon receptor: a potential mechanism for smoking-associated hypoalphalipoproteinemia.

AIMS: Smokers have lower plasma concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) compared with nonsmokers. To determine the molecular basis of this observation, the effect of activation of the aryl hydrocarbon receptor (AhR) on apo A-I gene expression was examined. MAIN METHODS: HepG2 cells were treated with AhR receptor agonists benzo(a)pyrene (BaP) and CAY10465, and AhR receptor antagonist CAY10464 and apo A-I protein, mRNA levels and promoter activity were measured. The effect of nicotine on apo A-I protein secretion was also tested. Using a series or apo A-I gene promoter deletion constructs, a xenobiotic response element (XRE) was identified. KEY FINDINGS: Treatment of HepG2 cells with the AhR receptor agonists BaP and CAY10465, inhibited apo A-I protein synthesis while nicotine, which does not bind AhR had no effect. Benzo(a)pyrene treatment also suppressed apo A-I mRNA and gene promoter activity. Treatment of HepG2 cells with the AhR receptor antagonist CAY10464 reversed the suppressive effect of BaP on apo A-I gene expression. A putative xenobiotic response element (XRE) was identified between nucleotides -325 and -186 (relative to the transcriptional start site, +1). SIGNIFICANCE: These results suggest that the cigarette smoking related environmental contaminant BaP promotes hypoalphalipoproteinemia in part through activation of the hepatic AhR.