Biotin deficiency up-regulates TNF-α production in murine macrophages

Toshinobu Kuroishi, Yasuo Endo, Koji Muramoto, Shunji Sugawara

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-α production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-α levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-α were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-α expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-α production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-κB family or AP-1. The TNF-α induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-α production or that biotin excess down-regulates TNF-α production, suggesting that biotin status may influence inflammatory diseases.

Original languageEnglish
Pages (from-to)912-920
Number of pages9
JournalJournal of Leukocyte Biology
Volume83
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1

Keywords

  • Cytokine
  • Inflammation
  • Nutrition

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of 'Biotin deficiency up-regulates TNF-α production in murine macrophages'. Together they form a unique fingerprint.

Cite this