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AB0062 Trem-1 expression induced by vitamin D3 in human monocytes/macrophages
  1. J.D. Ji1,
  2. B. Lee2,
  3. T.-H. Kim2,
  4. E. Kwon2,
  5. S.J. Choi1,
  6. Y.H. Lee1,
  7. J. Sohn3,
  8. G.G. Song1
  1. 1Rheumatology, College of Medicine, Korea University
  2. 2The Hanyang University Hospital for Rheumatic Diseases, Hanyang University College of Medicine
  3. 3Department of Biochemistry, College of Medicine, Korea University, Seoul, Korea, Republic Of

Abstract

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

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