Arthritis Research & Therapy (Jul 2019)

Rheumatoid arthritis synovial fibroblasts promote TREM-1 expression in monocytes via COX-2/PGE2 pathway

  • Anping Peng,
  • Xinyi Lu,
  • Jun Huang,
  • Min He,
  • Jianhua Xu,
  • Hui Huang,
  • Qubo Chen

DOI
https://doi.org/10.1186/s13075-019-1954-3
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 11

Abstract

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Abstract Background Triggering receptor expressed on myeloid cells-1 (TREM-1) is inducible on monocyte/macrophages and neutrophils and amplifies the inflammatory response. The aim of this study was to determine whether rheumatoid arthritis synovial fibroblasts (RASF) promote the expression of TREM-1 in monocytes and its potential regulatory mechanism. Methods Synovial fluid and paired peripheral blood from rheumatoid arthritis (RA) patients were analyzed using flow cytometry. Expression of TREM-1 in monocytes was detected after co-culture with RASF, with or without pre-treatment with toll-like receptor (TLR) ligands. Whether RASF-regulated TREM-1 level in monocytes require direct cell contact or soluble factors was evaluated by transwell experiment. COX-2 expression and PGE2 secretion in RASF were determined by quantitative PCR (qPCR) and ELISA. RASF, with and without TLR ligand stimulation, were treated with COX-2 inhibitors, COX-2 siRNA (siCOX-2) or EP1–4 antagonists, and the resulting TREM-1 level in CD14+ monocytes was measured using flow cytometry. Results TREM-1 was highly expressed in CD14+ cells from peripheral blood and especially synovial fluid from RA patients. The expression of TREM-1 in monocytes was increased by co-culture with RASF. TLR-ligand-activated RASF further elevated TREM-1 level. Transwell assay indicated that soluble factors played a key role in RASF-promoted expression of TREM-1 in monocytes. RASF, with or without stimulation by TLR ligands, increased secretion of PGE2 in a cyclooxygenase (COX)-2-dependent manner. PGE2 enhanced the increase in TREM-1 level in monocytes. Finally, studies using COX-2 inhibitors, COX-2 siRNA (siCOX-2) and EP1–4 antagonists, showed that RASF promotion of TREM-1 expression in monocytes was mediated by COX-2/PGE2/EP2,4 signaling. Conclusions Our data is the first report to reveal the critical role of RASF in upregulating TREM-1 expression in monocytes, which indicates that TREM-1 might be a novel target for RA therapy.

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