Background 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 plays a role as an amplifier of immune response. Recent studies suggested that TREM-1 may play an important role in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). TREM-1 expression is strongly upregulated by inflammatory stimuli such as lipopolysaccharide (LPS) and prostaglandin E2 (PGE2).
Objectives In this study, we investigated the regulation of TREM1 expression in human monocyte/macrophages. Also, we examined the effects of vitamin D3 on TREM-1 expression in human monocyte/macrophages.
Methods Gene expressions were analyzed using real-time PCR and cell surface expression of TREM-1 was analyzed by flow cytometry.
Results In human peripheral monocytes, TREM-1 is highly expressed and TREM-1 expression is down-regulated during differentiation into macrophages. In these cells, lipopolysaccharide (LPS) and TNFa, but not IL-1b stimulate TREM-1 expression. In addition to inflammatory molecules such as LPS and TNFa, 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)strongly upregulated the expression of TREM-1 in human monocyte/macrophages. Also TREM-1 expression was upregulated by 1,25(OH)2D3 in synovial fluid macrophages from RA patients. We found that 1,25(OH)2D3 stimulates TREM-1 mRNA expression by augmenting transcription, not by inhibiting mRNA degradation. The upregulated expression of TREM-1 by 1,25(OH)2D3 was partially dependent on p38 MAPK and NF-κB activation, and required new protein synthesis. Finally, 1,25(OH)2D3 augments TREM-1-stimulated IL-1β expression in the presence of LPS suggesting that vitamin D3-induced TREM-1 is functional.
Conclusions Our results show that 1,25(OH)2D3 can affect the innate and inflammatory responses by up-regulating TREM-1 expression, and suggest the possibility that 1,25(OH)2D3 may be function as an enhancer of innate immune response in chronic inflammatory conditions.
Disclosure of Interest None Declared