TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines.
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.
Kuai
Jun
J
Department of Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Gregory
Bernard
B
Hill
Andrew
A
Pittman
Debra D
DD
Feldman
Jeffrey L
JL
Brown
Tom
T
Carito
Brenda
B
O'Toole
Margot
M
Ramsey
Renee
R
Adolfsson
Oskar
O
Shields
Kathleen M
KM
Dower
Ken
K
Hall
J Perry
JP
Kurdi
Yahya
Y
Beech
Jonathan T
JT
Nanchahal
Jagdeep
J
Feldmann
Marc
M
Foxwell
Brian M
BM
Brennan
Fionula M
FM
Winkler
David G
DG
Lin
Lih-Ling
LL
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
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