Abstract
We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.
Original language | English |
---|---|
Pages (from-to) | 22593-8 |
Number of pages | 6 |
Journal | National Academy of Sciences. Proceedings |
Volume | 107 |
Issue number | 52 |
DOIs | |
Publication status | Published - 28 Dec 2010 |
Keywords
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
- Antimicrobial Cationic Peptides
- Blotting, Western
- Calcitriol
- Cells, Cultured
- Cytokines
- Gene Expression
- Humans
- Interferon-gamma
- Interleukin-4
- Monocytes
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Steroid Hydroxylases
- T-Lymphocytes
- Th1 Cells
- Th2 Cells
- Toll-Like Receptor 1
- Toll-Like Receptor 2
- Vitamin D
- Vitamin D3 24-Hydroxylase
- beta-Defensins