Biotin-deficiency up-regulates TNF-a production in vivo and in vitro

Abstract

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze indispensable cellular metabolism. It was reported that the concentrations of biotin were significantly lower in sera of patients with chronic inflammatory diseases. However, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin-deficiency on tumor necrosis factor (TNF)-α production in vivo and in vitro. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. After intravenous administration of lipopolysaccharide (LPS), serum TNF-α levels in biotin-deficient mice were significantly higher than those in biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in biotin-sufficient or biotin-deficient medium. Biotindefi cient J774.1 cells produced TNF-α significantly higher than biotin-sufficient J774.1 cells in response to LPS and even without LPS stimulation. Moreover, biotin-supplementation inhibited TNF-α production of biotin-deficient cells. Addition of cyclic guanosine 5′-monophosphate (cGMP) significantly decreased TNF-α production of the biotin-deficient cells, indicating that up-regulation of TNF-α production was regulated by cGMP-dependent signaling pathways. In conclusion, these results suggest that biotin is critically involved in inflammatory diseases via the regulation of TNF-α production in vivo and in vitro.