title: Intervention of an inflammation amplifier, triggering receptor expressed on myeloid cells 1, for treatment of autoimmune arthritis.
abstract: OBJECTIVE
  Triggering receptor expressed on myeloid cells 1 (TREM-1) is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in disease related to bacterial infections. Its blockade rescues the hosts in murine models of sepsis, to clear the bacteria without impairing the host defense. The aim of this study was to investigate the involvement of TREM-1 in an autoimmune, noninfectious disease.
  
  
  METHODS
  Synovial tissue specimens from the joints of patients with rheumatoid arthritis (RA) and the joints of mice with collagen-induced arthritis (CIA) were examined for TREM-1 expression, using flow cytometric analysis. Expression of TREM-1 on macrophages was induced by lipopolysaccharide, with or without a cyclooxygenase inhibitor. Rheumatoid synovial cells were stimulated with agonistic anti-TREM-1 antibodies. Recombinant adenovirus encoding the extracellular domain of TREM-1 fused with IgG-Fc (AxCATREM-1 Ig) or synthetic TREM-1 antagonistic peptides were injected to treat CIA, and the clinical manifestations of the antigen-specific T cell and B cell responses were evaluated.
  
  
  RESULTS
  TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with CIA. Unlike murine macrophages, human monocyte/macrophages did not depend on prostaglandin E2 for up-regulation of TREM-1. Agonistic anti-TREM-1 antibodies promoted tumor necrosis factor alpha production from rheumatoid synovial cells. Blockade of TREM-1 using AxCATREM-1 Ig and antagonistic peptides ameliorated CIA without affecting the serum levels of anti-type II collagen antibodies or the proliferative responses of splenocytes to type II collagen.
  
  
  CONCLUSIONS
  TREM-1 ligation contributes to the pathology of autoimmune arthritis. The results of this study implied that blockade of TREM-1 could be a new approach to rheumatic diseases that is safer than the presently available immunosuppressive treatments.
authors.affiliation: Tokyo Medical and Dental University, Department of Medicine and Rheumatology, Graduate School, Tokyo, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Tohru
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Toyomoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation
chemical_list: D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D010455:Peptides; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015232:Dinoprostone