Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human monocytes/macrophages

• We examined the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on TREM-1 expression.
• 1,25(OH)2D3 increased TREM-1 expression in human monocytes/macrophages.
• 1,25(OH)2D3 modulates the innate immune responses by increasing TREM-1 expression.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface receptor that is expressed mainly on monocytes and neutrophils, and acts as an amplifier of immune responses. In this study, 1,25(OH)2D3 strongly upregulated the expression of TREM-1 in human monocytes and macrophages. 1,25(OH)2D3 stimulated TREM-1 mRNA expression by augmenting transcription, and not by inhibiting mRNA degradation. The upregulated expression of TREM-1 by 1,25(OH)2D3 was dependent on the NF-κB signaling pathway and required new protein synthesis in differentiated U937 macrophages. Our results show that 1,25(OH)2D3 can affect the innate and inflammatory responses by upregulating TREM-1 expression, and suggest that 1,25(OH)2D3 may function as an enhancer of the innate immune response by upregulating TREM-1 expression, in addition to inducing the antimicrobial peptide cathelicidin.