期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 24, 期 12, 页码 2138-2143出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2013.08.005
关键词
Pyridoxal 5 ' phosphate; Shingosine 1 phosphate; Inflammation; Colitis; Colon
资金
- NIH [5-K05-CA100048-05]
- Prevent Cancer Foundation
- US Department of Agriculture [58-1950-7-707]
Pyridoxal-5-phosphate, the biologically active form of vitamin B-6, is a cofactor for over 140 biochemical reactions. Although severe vitamin B-6 deficiency is rare, mild inadequacy [plasma pyridoxal 5'-phosphate (PLP) <20 nmol/L] is observed in 19-27% of the US population. Plasma PLP concentrations are inversely related to markers of inflammation such as C-reactive protein. Furthermore, plasma PLP is diminished in those with inflammatory conditions and, in the case of inflammatory bowel disease (IBD), more so in those with active versus quiescent disease. Restricting B-6 intake attenuates IBD pathology in mice; however, the effects of supplementation are unclear. We therefore sought to determine the effects of mild inadequacy and moderate supplementation of B-6 on the severity of colonic inflammation. Weanling IL-10(-/-) (positive for Helicobacter hepaticus) mice were fed diets containing 0.5 (deficient), 6.0 (replete) or 24 (supplemented) mg/kg pyridoxine HCl for 12 weeks and then assessed for histological and molecular markers of colonic inflammation. Both low and high plasma PLP were associated with a significant suppression of molecular (TNF alpha, IL-6, IFN-gamma, COX-2 and iNOS expression) and histological markers of inflammation in the colon. PLP is required for the breakdown of sphingosine 1-phosphate (SIP), a chemotactic lipid, by SIP lyase. Colonic concentrations of SIP and PLP were significantly and inversely correlated. If confirmed, vitamin B-6 supplementation may offer an additional tool for the management of IBD. Although B-6 is required in dozens of reactions, its role in the breakdown of SIP may explain the biphasic relationship observed between PLP and inflammation. (C) 2013 Elsevier Inc. All rights reserved.
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