title: TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines.
abstract: OBJECTIVE
  To investigate the expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) in the synovium of human RA patients as well as the level of soluble TREM-1 in the plasma of RA patients.
  
  
  METHODS
  Twenty-four RA synovial samples were analysed by gene expression oligonucleotide microarrays. Expression levels of TREM-1 mRNA in murine CIA paws were determined by quantitative PCR (qPCR). TREM-1 protein expression was detected by immunohistochemistry in five RA synovial samples and two OA synovial samples. TREM-1-positive cells from five RA synovial tissues were analysed by FACS staining to determine the cell type. Activation of TREM-1 was tested in five RA synovial samples. Soluble TREM-1 was measured in serum from 32 RA patients.
  
  
  RESULTS
  The expression of TREM-1 mRNA was found to increase 6.5-fold in RA synovial samples, whereas it was increased 132-fold in CIA paws. Increased numbers of TREM-1-positive cells were seen in RA synovium sections and these cells co-expressed CD14. Using a TREM-1-activating cross-linking antibody in RA synovial cultures, multiple pro-inflammatory cytokines were induced. The average amount of soluble TREM-1 in plasma from RA patients was found to be higher than that in plasma from healthy volunteers.
  
  
  CONCLUSIONS
  These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.
authors.affiliation: Department of Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Kuai
authors.forename: Bernard
authors.initials: B
authors.lastname: Gregory
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Debra D
authors.initials: DD
authors.lastname: Pittman
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Feldman
authors.forename: Tom
authors.initials: T
authors.lastname: Brown
authors.forename: Brenda
authors.initials: B
authors.lastname: Carito
authors.forename: Margot
authors.initials: M
authors.lastname: O'Toole
authors.forename: Renee
authors.initials: R
authors.lastname: Ramsey
authors.forename: Oskar
authors.initials: O
authors.lastname: Adolfsson
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Shields
authors.forename: Ken
authors.initials: K
authors.lastname: Dower
authors.forename: J Perry
authors.initials: JP
authors.lastname: Hall
authors.forename: Yahya
authors.initials: Y
authors.lastname: Kurdi
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Beech
authors.forename: Jagdeep
authors.initials: J
authors.lastname: Nanchahal
authors.forename: Marc
authors.initials: M
authors.lastname: Feldmann
authors.forename: Brian M
authors.initials: BM
authors.lastname: Foxwell
authors.forename: Fionula M
authors.initials: FM
authors.lastname: Brennan
authors.forename: David G
authors.initials: DG
authors.lastname: Winkler
authors.forename: Lih-Ling
authors.initials: LL
authors.lastname: Lin
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1