title: Biotin deficiency enhances the inflammatory response of human dendritic cells.
abstract: The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, California;
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, California; aagrawal@uci.edu.
authors.forename: Anshu
authors.identifier: 0000-0002-3323-9152
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Medicine, Department of Physiology and Biophysics, University of California, Irvine, California; and Veterans Affairs Medical Center-151, Long Beach, California.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D001710:Biotin / Q000378:metabolism*; D028921:Biotinidase Deficiency / Q000378:metabolism / Q000473:pathology*; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D053759:Interleukin-23; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001710:Biotin; D007371:Interferon-gamma
keywords: biotin; dendritic cells; human; inflammation